term effectiveness and cost of a systematic care management program for bipolar disorder. *Archives of General Psychiatry*, Vol. 63, No.5, pp. 500-508, ISSN 0003990X Simon, G. E.; Ludman, E. J.; Unützer, J.; Bauer, M. S.; Operskalski, B. & Rutter, C. (Jan 2005).

Randomized trial of a population-based care program for people with bipolar

Bipolar Interactive Psychoeducation (BIPED) study: trial design and protocol, In:

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(2001). The Stanley Foundation Bipolar Treatment Outcome Network: II. Demographics and illness characteristics of the first 261 patients. *Journal of Affective*

(Nov 2005). Suicidal ideation and attempts in bipolar I and II disorders. *Journal of*

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Perlick, D. A.; Rosenheck, R. A.; Miklowitz, D. J.; Kaczynski, R.; Link, B.; Ketter, T. et al. (Jun

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http://www.biomedcentral.com/1471-244X/9/50.

**14**

*India*

Sangita Saini1,

Anil Shandil2 and S. K. Singh3

*Technology, Hisar, Haryana*

*2L.L.R.M Medical College, Meerut, U.P 3Guru Jambheshwar University of Science and*

**Recent Therapies in Depression**

Depression is a significant health problem. It affects men and women of all ages and social backgrounds. Around one in five of the population of world will experience depression at some point in their lives. Prevalence is higher in women than men. It can range in severity from a mild disturbance to a severe illness with a high risk of suicide. The impact of the disorder will also be experienced by family, friends and colleagues. In 2006/07 there were around 500,000 general practitioner consultations with depression and other affective disorders. Over half of those with depression do not seek formal treatment. As well as the personal and social consequences of depression there are also negative economic effects. Depression is associated with sickness absence and prevents many people seeking, maintaining or returning to employment. In an economic analysis the total loss of output due to depression and chronic anxiety in England in 2002/3 was estimated at £12 billion.5. The most common intervention for depression is prescribed antidepressant medication. Managing depression in the primary care and general practice setting is challenging. The

The use of pharmacological agents often enables the physician to circumvent time constraints. Difficulties arise when knowledge about the properties and use of these agents is lacking. The other factor that often hinders the management of the depressed patient is that psychological and social issues are inadequately addressed. Psychological and social interventions should accompany pharmacological therapy in order to bring about remission of symptoms in the depressed patient. Appropriate management of depression requires knowledge of the severity and type of depressive disorders. Depressive disorders can be categorised as mild, moderate or severe. Severe depression can result in psychosis. A chronic mild to moderate depression lasting more than two years is termed dysthymia. Depression can also be part of bipolar disorder. There is a variation in the management of

**1. Introduction**

common reasons leading to this challenge are:

Insufficient training at the undergraduate level

The constraints of time

each of the above.

Somatisation of symptoms

*1P.D.M. College of Pharmacy, Bahadurgarh, Haryana*

 http://www.everydayhealth.com/bipolar-disorder/cognitive-behavioral-therapyfor-bipolar-disorder.aspx

## **Recent Therapies in Depression**

Sangita Saini1,

Anil Shandil2 and S. K. Singh3 *1P.D.M. College of Pharmacy, Bahadurgarh, Haryana 2L.L.R.M Medical College, Meerut, U.P 3Guru Jambheshwar University of Science and Technology, Hisar, Haryana India*

#### **1. Introduction**

344 Clinical, Research and Treatment Approaches to Affective Disorders

Vieta, E. (2005). Improving treatment adherence in bipolar disorder through

Vieta, E.; Günther, O.; Locklea,R. J.; Ekman, M.; Miltenburger, C.; Chatterton, M. L. et al.

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Wheeler, R. B. (Jul 2010a). Psychoeducation Therapy for Bipolar Disorder. In: *Everyday*

http://www.everydayhealth.com/bipolar-disorder/psychoeducation-therapy-for-

Wheeler, R. B. (Jul 2010b). Cognitive-Behavioral Therapy for Bipolar. In: *Everyday Health,*

http://www.everydayhealth.com/bipolar-disorder/cognitive-behavioral-therapy-

*and Alcohol Dependence*, Vol. 104, No.3, pp. 212–219, ISSN 0376-8716

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bipolar-disorder.aspx

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for-bipolar-disorder.aspx

psychoeducation. *Journal of Clinical Psychiatry*. Vol. 66, Supplement 1, pp. 24-29,

(Sep 2011). Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials. *International Journal of Neuropsychopharmacology*, Vol. 14, No. 8, pp. 1029-1049, ISSN 1461-1457 Volkmar, F. R.; Bacon, S.; Shakir, S. A. & Pfefferbaum, A. (1981). Group therapy in the

management of manic-depressive illness. *American Journal of Psychotherapy*, Vol. 35,

"community-friendly" version of Integrated Group Therapy for patients with bipolar disorder and substance dependence: A randomized controlled trial. *Drug*

al. (2007). A randomized trial of integrated group therapy versus group drug counseling for patients with bipolar disorder and substance dependence. *American*

> Depression is a significant health problem. It affects men and women of all ages and social backgrounds. Around one in five of the population of world will experience depression at some point in their lives. Prevalence is higher in women than men. It can range in severity from a mild disturbance to a severe illness with a high risk of suicide. The impact of the disorder will also be experienced by family, friends and colleagues. In 2006/07 there were around 500,000 general practitioner consultations with depression and other affective disorders. Over half of those with depression do not seek formal treatment. As well as the personal and social consequences of depression there are also negative economic effects. Depression is associated with sickness absence and prevents many people seeking, maintaining or returning to employment. In an economic analysis the total loss of output due to depression and chronic anxiety in England in 2002/3 was estimated at £12 billion.5. The most common intervention for depression is prescribed antidepressant medication. Managing depression in the primary care and general practice setting is challenging. The common reasons leading to this challenge are:

The use of pharmacological agents often enables the physician to circumvent time constraints. Difficulties arise when knowledge about the properties and use of these agents is lacking. The other factor that often hinders the management of the depressed patient is that psychological and social issues are inadequately addressed. Psychological and social interventions should accompany pharmacological therapy in order to bring about remission of symptoms in the depressed patient. Appropriate management of depression requires knowledge of the severity and type of depressive disorders. Depressive disorders can be categorised as mild, moderate or severe. Severe depression can result in psychosis. A chronic mild to moderate depression lasting more than two years is termed dysthymia. Depression can also be part of bipolar disorder. There is a variation in the management of each of the above.

Recent Therapies in Depression 347

Although there are some studies comparing psychological therapies for depression, the majority of studies involve comparisons of psychological therapies with prescribed antidepressant medication treatment. There is very less evidence to support detailed recommendations on the number of therapy sessions required for efficacy, maintenance of effect or prevention of relapse. Practitioners delivering psychological therapies should be trained to approve levels of competency, participate in continuing professional development and be registered with the appropriate governing body. Several types of psychotherapy are used in individual and group settings and with families. Patients must be medically stable to be able to participate meaningfully in any type of psychological therapy. Thus, a patient who has required hospitalization for refeeding and to stabilize his/her medical condition will ordinarily not be able to participate in therapy until after he/she has recovered sufficiently to enable cognitive function to return to normal. A given psychologist or psychiatrist may use several different approaches tailored to the situation. Two types of psychotherapy used for the patient with stabilized medical condition; Cognitive behavior

Cognitive therapy is the most extensively researched psychological treatment for nonpsychotic unipolar outpatient depressive disorders.This is a type of psychotherapeutic treatment that attempts to change a patient's feelings and behaviors by changing the way

**2. Self help**

Exercise

Folate

Inositol

Acupuncture

Homeopathy Light therapy Massage therapy

Yoga

Guided self help Computerised self help

Self help support groups

Lifestyle modification

**3. Exercise and lifestyle modification**

*Hypericum*extract (St John's wort)

Polyunsaturated fatty acids S-adenosyl-L-methionine

Animal assisted therapy

**2. Psychological therapies 2.1 Psychological therapies**

therapy (CBT) and behavior therapy (BT)

**4. Herbal remedies and nutritional supplements**

Other nutritional supplements and herbal remedies

**5. Complementary and alternative therapies**

Mild depression can be handled in primary care and does not need pharmacological therapy. The watchful waiting, guided self-help, exercise and brief psychological interventions. Moderate to severe depression can also be handled in the primary care setting with medication, psychological interventions and social support. Severe depression with psychosis and risk of suicide, recurrent atypical and treatment-resistant depression should be managed by mental health specialists.

#### **Therapies used to treat depression has been divided into parts**

#### **Pharmacological**

The drugs used in mental depression are classified as

	- a. Tricyclic antidepressant eg imipramine, despiramine, amitriptyline, nortryptyline, doxepine, clomipramine, trimipramine
	- b. Monoamine oxidase inhibitors egPhanalzine, Pargyline
	- c. Lithium carbonate (antimanic drug)
	- a. Selective serotonin reuptake inhibitors
	- b. Selective norepinephrine reuptake inhibitors
	- c. Serotonin norepinephrine reuptake inhibitors
	- d. Atypical antidepressants
	- e. Reversible inhibitors of MAO-A

#### **Non pharmacological**

Non pharmacological can be sub divided into three therapies

#### **1. Psychological therapies**

Behavioural activation Cognitive behavioural therapy Counselling Couple-focused therapy Family therapy Hypnotherapy Interpersonal therapy Mindfulness based cognitive therapy Music therapy Problem solving therapy Psychodynamic psychotherapy Reminiscence therapy Other psychological therapies Common factors in psychological therapies

#### **2. Self help**

346 Clinical, Research and Treatment Approaches to Affective Disorders

Mild depression can be handled in primary care and does not need pharmacological therapy. The watchful waiting, guided self-help, exercise and brief psychological interventions. Moderate to severe depression can also be handled in the primary care setting with medication, psychological interventions and social support. Severe depression with psychosis and risk of suicide, recurrent atypical and treatment-resistant depression should

a. Tricyclic antidepressant eg imipramine, despiramine, amitriptyline, nortryptyline,

be managed by mental health specialists.

1. First generation antidepressants

2. Second generation antidepressants

d. Atypical antidepressants e. Reversible inhibitors of MAO-A

**Non pharmacological**

2. Self help

Counselling

Family therapy Hypnotherapy Interpersonal therapy

Music therapy

1. Psychological therapy

3. Structured exercise **1. Psychological therapies**

Behavioural activation

Couple-focused therapy

Problem solving therapy Psychodynamic psychotherapy

Other psychological therapies

Reminiscence therapy

Cognitive behavioural therapy

Mindfulness based cognitive therapy

Common factors in psychological therapies

i. Pharmacological ii. Non-Pharmacological

**Pharmacological**

**Therapies used to treat depression has been divided into parts**

The drugs used in mental depression are classified as

doxepine, clomipramine, trimipramine

Non pharmacological can be sub divided into three therapies

c. Lithium carbonate (antimanic drug)

a. Selective serotonin reuptake inhibitors b. Selective norepinephrine reuptake inhibitors c. Serotonin norepinephrine reuptake inhibitors

b. Monoamine oxidase inhibitors egPhanalzine, Pargyline

Self help support groups Guided self help Computerised self help

#### **3. Exercise and lifestyle modification**

Exercise Lifestyle modification

#### **4. Herbal remedies and nutritional supplements**

Folate *Hypericum*extract (St John's wort) Inositol Polyunsaturated fatty acids S-adenosyl-L-methionine Other nutritional supplements and herbal remedies

#### **5. Complementary and alternative therapies**

Acupuncture Animal assisted therapy Homeopathy Light therapy Massage therapy Yoga

#### **2. Psychological therapies**

#### **2.1 Psychological therapies**

Although there are some studies comparing psychological therapies for depression, the majority of studies involve comparisons of psychological therapies with prescribed antidepressant medication treatment. There is very less evidence to support detailed recommendations on the number of therapy sessions required for efficacy, maintenance of effect or prevention of relapse. Practitioners delivering psychological therapies should be trained to approve levels of competency, participate in continuing professional development and be registered with the appropriate governing body. Several types of psychotherapy are used in individual and group settings and with families. Patients must be medically stable to be able to participate meaningfully in any type of psychological therapy. Thus, a patient who has required hospitalization for refeeding and to stabilize his/her medical condition will ordinarily not be able to participate in therapy until after he/she has recovered sufficiently to enable cognitive function to return to normal. A given psychologist or psychiatrist may use several different approaches tailored to the situation. Two types of psychotherapy used for the patient with stabilized medical condition; Cognitive behavior therapy (CBT) and behavior therapy (BT)

Cognitive therapy is the most extensively researched psychological treatment for nonpsychotic unipolar outpatient depressive disorders.This is a type of psychotherapeutic treatment that attempts to change a patient's feelings and behaviors by changing the way

Recent Therapies in Depression 349

interpersonal context linked to depression. A review identified eight studies evaluating the effect of marital therapy on depression. A variety of treatment models were subsumed within the marital therapy approach, including CBT, emotion-focused, interpersonal and systemic therapy. A variety of control comparisons were used, including CBT, interpersonal therapy, drug therapy, combined individual and drug therapy. Duration of treatment ranged from 10-20 weeks and follow up ranged from post-test to two years. Studies were characterised by small sample size, lack of intention to treat analysis and high numbers lost to follow up. The review concluded there was no evidence to support marital therapy being any more or less effective than one to one therapies or drug therapy in the treatment of depression, even when associated with marital distress. In comparison to no/minimal treatment the outcome for depression was better in the marital therapy group, although this was based on only two small studies.A couple-focused approach should be considered where the current relationship is contributing to the depression, or where involvement of a

Family therapy helps people in a close relationship help each other. It enables family members to express and explore difficult thoughts and emotions safely, to understand each other's experiences and views, appreciate each other's needs, build on family strengths and

Hypnosis is used in this therapy as main techniques. When Cognitive Behaviour Therapy supplemented by hypnotherapy produced a significantly larger reduction in depressive

A time-limited intervention, which aims to reduce symptoms by working on improving the quality of the patient's interpersonal relationships. IPT focuses on specific interpersonal problem areas such as grief, role transition and interpersonal disputes. A positive therapeutic alliance is encouraged and a range of therapeutic strategies are employed to encourage the open expression of affect and problem resolution. Patient literacy is not required. A study examining achievement of complete remission in major depression found

A therapeutic approach where music-making forms the primary basis for communication. A review of five small, diverse and poor quality studies concluded that music therapy on its own or as an adjunct to psychological therapies, is acceptable to people with depression and is associated with improvements in mood. The small number and poor methodological

A brief focused psychological intervention that is delivered by an individual trained in problem solving approaches. These are often highly individualised and have a pragmatic focus, in which the professional and individual work through a series of defined steps to clarify the person's problems, desired goals, generate potential solutions and help to

quality of studies mean that it is not possible to be confident about its effectiveness.

that interpersonal therapy (IPT), CBT and medication were equally effective.

partner is considered to be of potential therapeutic benefit.

make useful changes in their relationships and their lives.

**Family therapy**

**Hypnotherapy**

**Music therapy**

**Problem solving therapy**

implement the chosen solution

symptoms than CBT alone.

**Interpersonal therapy**

the patient thinks about or perceives his/her significant life experiences whereas behavior Therapy (BT) is a type of psychotherapy that uses principles of learning to increase the frequency of desired behaviors and/or decrease the frequency of problem behaviors. A meta-analysis of 16 studies found behavioural activation to be effective in reducing depressive symptoms in adults and older adults compared to treatment as usual and waiting list control, and as effective as cognitive therapy. This is consistent with the conclusions of a study incorporating behavioural activation therapy as part of a larger metaanalysis specifically in patients aged over 50 with depression.

Denmen concluded that cognitive behavior therapy was more effective than behavior therapy, other psychotherapies, and pharmacotherapy. An important advantage to cognitive behavior therapy might be in treating depression in patients with personality disorder, who are recognized as responding less well to all forms of therapy.

The cognitive and behavioral therapies have evolved as an alternative to more traditional nondirective and insight oriented modes of psychotherapy. The family of cognitive and behavioral therapies includes a diverse group of interventions. Nevertheless, the treatments shareseveral pragmatic and theoretical assumptions. First, these therapies emphasize psychoeducation: patients learn about the nature of their difficulties and are providedreasons for use of particular treatment strategies. Second, the cognitive and behavioral therapies typically employ homework and self-help assignments to provide patients theopportunity to practice therapeutic methods that enhance the generalization of newly acquired skills outside of the therapy hour. Third, objective assessment of psychiatricillness is an integral part of treatment, and the selection of therapeutic strategies derives logically from such assessments. Fourth, the therapeutic methods used are structured and directive, and as such require a high level of therapist activity (often they are described in treatment manuals). Fifth, for most disorders, the cognitive and behavioral therapies are time-limited interventions. Sixth, and perhaps most important, these therapies are built on empirical evidence that validates their theoretical orientation and guides the choice of therapeutic techniques. Specifically, learning theories (i.e., classical, operant, and observational models of learning) and the principles of cognitive psychology are relied on heavily in constructing cognitive–behavioral treatment models.

#### **Counselling**

Counselling is the skilled and principled use of relationships which develop self knowledge, emotional acceptance and growth, and personal resources. The overall aim is to live more fully and satisfyingly. Counselling may be concerned with addressing and resolving specific problems, making decisions, coping with crises, working through inner feelings and inner conflict, or improving relationships with others. The counsellor's role is to facilitate the patient's work in ways that respect the patient's values, personal resources, and capacity for self determination.

During a study of 12 months on the patient, counselling was as effective as antidepressants but antidepressants may result in more rapid recovery and are likely to be chosen by those who are more severely depressed.

#### **Couple-focused therapy**

Couple-focused therapy has the twofold aim of modifying negative interaction patterns and increasing mutually supportive aspects of couple relationships, thus changing the

the patient thinks about or perceives his/her significant life experiences whereas behavior Therapy (BT) is a type of psychotherapy that uses principles of learning to increase the frequency of desired behaviors and/or decrease the frequency of problem behaviors. A meta-analysis of 16 studies found behavioural activation to be effective in reducing depressive symptoms in adults and older adults compared to treatment as usual and waiting list control, and as effective as cognitive therapy. This is consistent with the conclusions of a study incorporating behavioural activation therapy as part of a larger meta-

Denmen concluded that cognitive behavior therapy was more effective than behavior therapy, other psychotherapies, and pharmacotherapy. An important advantage to cognitive behavior therapy might be in treating depression in patients with personality

The cognitive and behavioral therapies have evolved as an alternative to more traditional nondirective and insight oriented modes of psychotherapy. The family of cognitive and behavioral therapies includes a diverse group of interventions. Nevertheless, the treatments shareseveral pragmatic and theoretical assumptions. First, these therapies emphasize psychoeducation: patients learn about the nature of their difficulties and are providedreasons for use of particular treatment strategies. Second, the cognitive and behavioral therapies typically employ homework and self-help assignments to provide patients theopportunity to practice therapeutic methods that enhance the generalization of newly acquired skills outside of the therapy hour. Third, objective assessment of psychiatricillness is an integral part of treatment, and the selection of therapeutic strategies derives logically from such assessments. Fourth, the therapeutic methods used are structured and directive, and as such require a high level of therapist activity (often they are described in treatment manuals). Fifth, for most disorders, the cognitive and behavioral therapies are time-limited interventions. Sixth, and perhaps most important, these therapies are built on empirical evidence that validates their theoretical orientation and guides the choice of therapeutic techniques. Specifically, learning theories (i.e., classical, operant, and observational models of learning) and the principles of cognitive psychology are relied on

Counselling is the skilled and principled use of relationships which develop self knowledge, emotional acceptance and growth, and personal resources. The overall aim is to live more fully and satisfyingly. Counselling may be concerned with addressing and resolving specific problems, making decisions, coping with crises, working through inner feelings and inner conflict, or improving relationships with others. The counsellor's role is to facilitate the patient's work in ways that respect the patient's values, personal resources, and capacity for

During a study of 12 months on the patient, counselling was as effective as antidepressants but antidepressants may result in more rapid recovery and are likely to be chosen by those

Couple-focused therapy has the twofold aim of modifying negative interaction patterns and increasing mutually supportive aspects of couple relationships, thus changing the

disorder, who are recognized as responding less well to all forms of therapy.

analysis specifically in patients aged over 50 with depression.

heavily in constructing cognitive–behavioral treatment models.

**Counselling**

self determination.

who are more severely depressed.

**Couple-focused therapy**

interpersonal context linked to depression. A review identified eight studies evaluating the effect of marital therapy on depression. A variety of treatment models were subsumed within the marital therapy approach, including CBT, emotion-focused, interpersonal and systemic therapy. A variety of control comparisons were used, including CBT, interpersonal therapy, drug therapy, combined individual and drug therapy. Duration of treatment ranged from 10-20 weeks and follow up ranged from post-test to two years. Studies were characterised by small sample size, lack of intention to treat analysis and high numbers lost to follow up. The review concluded there was no evidence to support marital therapy being any more or less effective than one to one therapies or drug therapy in the treatment of depression, even when associated with marital distress. In comparison to no/minimal treatment the outcome for depression was better in the marital therapy group, although this was based on only two small studies.A couple-focused approach should be considered where the current relationship is contributing to the depression, or where involvement of a partner is considered to be of potential therapeutic benefit.

#### **Family therapy**

Family therapy helps people in a close relationship help each other. It enables family members to express and explore difficult thoughts and emotions safely, to understand each other's experiences and views, appreciate each other's needs, build on family strengths and make useful changes in their relationships and their lives.

#### **Hypnotherapy**

Hypnosis is used in this therapy as main techniques. When Cognitive Behaviour Therapy supplemented by hypnotherapy produced a significantly larger reduction in depressive symptoms than CBT alone.

#### **Interpersonal therapy**

A time-limited intervention, which aims to reduce symptoms by working on improving the quality of the patient's interpersonal relationships. IPT focuses on specific interpersonal problem areas such as grief, role transition and interpersonal disputes. A positive therapeutic alliance is encouraged and a range of therapeutic strategies are employed to encourage the open expression of affect and problem resolution. Patient literacy is not required. A study examining achievement of complete remission in major depression found that interpersonal therapy (IPT), CBT and medication were equally effective.

#### **Music therapy**

A therapeutic approach where music-making forms the primary basis for communication. A review of five small, diverse and poor quality studies concluded that music therapy on its own or as an adjunct to psychological therapies, is acceptable to people with depression and is associated with improvements in mood. The small number and poor methodological quality of studies mean that it is not possible to be confident about its effectiveness.

#### **Problem solving therapy**

A brief focused psychological intervention that is delivered by an individual trained in problem solving approaches. These are often highly individualised and have a pragmatic focus, in which the professional and individual work through a series of defined steps to clarify the person's problems, desired goals, generate potential solutions and help to implement the chosen solution

Recent Therapies in Depression 351

three or more times a week for 30-40 minutes at an intensity sufficient to provide an energy expenditure of 70-80% of heart rate reserve; this equates to the public health dose of

2. No good quality evidence was identified on the effect of reducing alcohol consumption

3. Examination of alcohol consumption as a causative factor in depression was outside the

4. Primary care interventions for patients with alcohol dependence, hazardous or harmful

5. reducing caffeine intakeNo good quality evidence was identified on the effects of

This section considers herbal remedies and nutritional supplements which have been subjected to evaluate their efficacy in the treatment of depression. They are not licensed medications and have not been subjected to the rigorous regulatory approval process required for prescription medications. In addition to this there are issues around quality

A well conducted systematic review of folate for depression was identified. There was only one study of folate as a stand-alone treatment for depression. This did not find significant

A perennial herb of the genus Hypericum.Inositol An isomer of glucose. It is a naturally occuring compound which is widely available as a dietary supplement. Polyunsaturated

"Essential fatty acids" that humans cannot synthesise de novo; intake is dependent on dietary sources such as fish and seafood. The examples most studied are the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). S-adenosyl-

(SAMe) A coenzyme involved in methyl group transfers. It is available as a nutritional supplement. Selenium A non-metallic element which rarely occurs in its elemental state in

A good quality systematic review of small, short term RCTs reported that current evidence

is unclear whether or not inositol is of benefit in the treatment of depression.

control and lack of standardisation of herbal remedies and nutritional supplements.

accumulating 30 minutes of moderate

1. reducing alcohol consumption

ondepressive symptoms.

*Hypericum* **extract (St John's Wort)**

drinkingare described in SIGN 74.62

reducing caffeine intake on depressivesymptoms.

**2.4 Herbal remedies and nutritional supplements**

7. good practice in lifestyle advice for patients with depression

scopeof the guideline.

**Lifestyle modification**

6. return to work

**Folate**

benefit.

fatty acids (PUFAs)

Lmethionine

nature. **Inositol**

#### **Psychodynamic psychotherapy**

Based on psychodynamic theories of development and of the mind and includes attention to unconscious as well as conscious mental processes. The approach places emphasis on the importance of the therapeutic relationship, including transference and counter transference, how difficulties from the past can be repeated in the therapeutic relationship as well as in current relationships and therefore understood and changed. The therapy involves both expressive and supportive elements.

#### **Reminiscence therapy**

Entails a progressive return to an awareness of past experiences, both successful and unsuccessful, so that salient life experiences may be re-examined and re-integrated. The life review process gives older people opportunities to place their accomplishments in perspective, to resolve lingering conflicts, and to find new significance and meaning in their lives, thereby relieving the despair and depression that often accompany ageing.

#### **2.2 Self help**

#### **Self help support groups**

There is no standard definition of support groups in the literature. No studies were identified on self help groups as a stand-alone intervention for patients with depression. Practitioners referring patients to self help groups should consider the following parameters of good practice:

Groups should be:

#### **Self help**

Computerised self help Online or computer based packages of self help material. Guided self help Self help interventions which incorporate some form of therapist support.Self help interventions Self help interventions cover a range of interactive packages,paper or webbased written self help materials.

#### **2.3 Exercise and lifestyle modification**

#### **Exercise**

Exercise is a subset of physical activity, which is any movement of the body that results in energy expenditure rising above resting level, and includes activities of daily living, domestic chores, gardening and walking whereas Structured exercise that is undertaken

Based on psychodynamic theories of development and of the mind and includes attention to unconscious as well as conscious mental processes. The approach places emphasis on the importance of the therapeutic relationship, including transference and counter transference, how difficulties from the past can be repeated in the therapeutic relationship as well as in current relationships and therefore understood and changed. The therapy involves both

Entails a progressive return to an awareness of past experiences, both successful and unsuccessful, so that salient life experiences may be re-examined and re-integrated. The life review process gives older people opportunities to place their accomplishments in perspective, to resolve lingering conflicts, and to find new significance and meaning in their

There is no standard definition of support groups in the literature. No studies were identified on self help groups as a stand-alone intervention for patients with depression. Practitioners referring patients to self help groups should consider the following parameters

recovery-focused and with clear confidentiality policies maintained by members and

led by facilitators who are trained in listening, conflict management and facilitation

Computerised self help Online or computer based packages of self help material. Guided self help Self help interventions which incorporate some form of therapist support.Self help interventions Self help interventions cover a range of interactive packages,paper or web-

Exercise is a subset of physical activity, which is any movement of the body that results in energy expenditure rising above resting level, and includes activities of daily living, domestic chores, gardening and walking whereas Structured exercise that is undertaken

lives, thereby relieving the despair and depression that often accompany ageing.

linked to an organisation or well established group that can offer the necessary

resources, support and promotion of the groups

held in accessible, non-stigmatising and welcoming venues

skills; and who are supervised and supported themselves.

subject to regular review and evaluation

**Psychodynamic psychotherapy**

expressive and supportive elements.

**Reminiscence therapy**

**Self help support groups**

**2.2 Self help**

of good practice: Groups should be:

facilitators

based written self help materials.

**2.3 Exercise and lifestyle modification**

**Self help**

**Exercise**

three or more times a week for 30-40 minutes at an intensity sufficient to provide an energy expenditure of 70-80% of heart rate reserve; this equates to the public health dose of accumulating 30 minutes of moderate

#### **Lifestyle modification**

#### **2.4 Herbal remedies and nutritional supplements**

This section considers herbal remedies and nutritional supplements which have been subjected to evaluate their efficacy in the treatment of depression. They are not licensed medications and have not been subjected to the rigorous regulatory approval process required for prescription medications. In addition to this there are issues around quality control and lack of standardisation of herbal remedies and nutritional supplements.

#### **Folate**

A well conducted systematic review of folate for depression was identified. There was only one study of folate as a stand-alone treatment for depression. This did not find significant benefit.

#### *Hypericum* **extract (St John's Wort)**

A perennial herb of the genus Hypericum.Inositol An isomer of glucose. It is a naturally occuring compound which is widely available as a dietary supplement. Polyunsaturated fatty acids (PUFAs)

"Essential fatty acids" that humans cannot synthesise de novo; intake is dependent on dietary sources such as fish and seafood. The examples most studied are the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). S-adenosyl-Lmethionine

(SAMe) A coenzyme involved in methyl group transfers. It is available as a nutritional supplement. Selenium A non-metallic element which rarely occurs in its elemental state in nature.

#### **Inositol**

A good quality systematic review of small, short term RCTs reported that current evidence is unclear whether or not inositol is of benefit in the treatment of depression.

Recent Therapies in Depression 353

Homeopathy A system of medicine which is based on treating the individual with highly diluted substances given mainly in tablet form, which trigger the body's natural system of

Treatment that involves regular use of a certain spectrum of lights in a light panel or light screen that bathes the person in that light. Light therapy is also used to treat conditions such

The manipulation of the soft tissues of the body - the muscles, tendons and ligaments. The therapeutic value of massage has been recorded in several studies. It has been shown to reduce stress and anxiety; relax muscles; aid in circulation, digestion, and excretion; and reduce pain perception. There are many different types of massage -- effleurage, deep tissue, and relaxation massage. Even the simplest massage may convey to the recipient a feeling of being cared for. Both maternal and infant massage have been evaluated in the treatment of

A therapy based on the use of very concentrated "essential" oils from the flowers, leaves, bark, branches, rind or roots of plants with purported healing properties. Aromatherapy involves the administration of pure essential oils of fragrant plants either through breathing the aromatic vapours using an aroma diffuser, or absorbing diluted oils through the skin in

An ancient system of breathing practices, physical exercises and postures, and meditation,

A hands-on alternative healing technique that involves the exchange of energy between

A Chinese exercise system that uses slow, smooth, body movements to achieve a state of relaxation of both body and mind. Thought field therapy Involves tapping with the fingers

In the present review, a number of drug and non-drug strategies group setting may be considered as a treatment option to reduce relapse in patients with depression who have

practitioner and patient to restore mental, physical, emotional, and spiritual balance.

intended to integrate the practitioner's body, mind, and spirit.

Involves massage of reflex areas found in the feet and the hands.

at meridian points on the upper body and hands.

**Homeopathy**

**Light therapy**

**Massage therapy**

postpartum depression.

a bath or during massage.

**Aromatherapy**

**Yoga**

**Reiki**

**Reflexology**

**3. Conclusion**

**T'ai Chi**

as seasonal affective disorder (seasonal depression).

healing.

#### **Polyunsaturated fatty acids**

Five systematic reviews of the use of polyunsaturated fatty acids (PUFAs) in the treatment of patients with depression were identified. Most trials included in the reviews examined the use of PUFAs as supplements to antidepressant medication with only two small RCTs examining the use of PUFAs as a stand-alone treatment of depression.

#### **s-adenosyl-L-methionine**

One well conducted systematic review of 28 small and heterogeneous studies found a modest benefit of S-adenosyl-L-methionine (SAMe) over placebo in the treatment of depression. There were no significant differences in outcome when SAMe was compared with tricyclic antidepressants.

#### **Chromium**

A mineral that humans require in trace amounts.Folate Folic acid and folate (the anionic form) are forms of the water soluble vitamin B9. These occur naturally in food and can also be taken as supplements.

#### **Ginseng**

A perennial plant which grows in eastern Asia. The root extract is widely available as a herbal remedy. Ginkgo biloba Ginkgo biloba, also known as the Maidenhair tree, is a unique species of tree, the fruits and seeds of which are used in traditional Chinese medicine. Leaf extracts are available as supplements.

#### **2.5 Complementary and alternative therapies**

#### **Acupuncture**

A family of procedures involving the stimulation of anatomical locations on or in the skin by a variety of techniques. There are a number of different approaches to diagnosis and treatment in acupuncture that incorporate medical traditions from China, Japan, Korea, and other countries. Depression is widely experienced in our communities. In clinical depression, people report a lack of interest in life and activities which they otherwise normally enjoy. This can be accompanied by other symptoms including weight loss, over-eating, feelings of uselessness, sleep disturbance, self neglect and social withdrawal, insomnia or hypersomnia (sleeping too much), loss of energy, low self esteem and poor concentration. Acupuncture has a long history of use in China and Japan. Traditional Chinese medicine theory describes a state of health maintained by a balance of energy in the body. Acupuncture involves the insertion of fine needles into different parts of the body to correct the imbalance of energy in the body. There are a range of styles of acupuncture from traditional/classical acupuncture, auricular acupuncture, trigger point acupuncture, and single point acupuncture.

#### **Animal assisted therapy**

A therapy that uses dogs or other pets to improve the physical and mental health of patients with certain acute or chronic diseases. There is evidence from one systematic review that the introduction of animal assisted activities may have beneficial effects on the severity of depressive symptoms in older people resident in nursing homes and psychiatric institutions. The degree to which the benefits found are a result of animal contact or human contact with the animal facilitator is unclear and requires further investigation.

#### **Homeopathy**

352 Clinical, Research and Treatment Approaches to Affective Disorders

Five systematic reviews of the use of polyunsaturated fatty acids (PUFAs) in the treatment of patients with depression were identified. Most trials included in the reviews examined the use of PUFAs as supplements to antidepressant medication with only two small RCTs

One well conducted systematic review of 28 small and heterogeneous studies found a modest benefit of S-adenosyl-L-methionine (SAMe) over placebo in the treatment of depression. There were no significant differences in outcome when SAMe was compared

A mineral that humans require in trace amounts.Folate Folic acid and folate (the anionic form) are forms of the water soluble vitamin B9. These occur naturally in food and can also

A perennial plant which grows in eastern Asia. The root extract is widely available as a herbal remedy. Ginkgo biloba Ginkgo biloba, also known as the Maidenhair tree, is a unique species of tree, the fruits and seeds of which are used in traditional Chinese medicine. Leaf

A family of procedures involving the stimulation of anatomical locations on or in the skin by a variety of techniques. There are a number of different approaches to diagnosis and treatment in acupuncture that incorporate medical traditions from China, Japan, Korea, and other countries. Depression is widely experienced in our communities. In clinical depression, people report a lack of interest in life and activities which they otherwise normally enjoy. This can be accompanied by other symptoms including weight loss, over-eating, feelings of uselessness, sleep disturbance, self neglect and social withdrawal, insomnia or hypersomnia (sleeping too much), loss of energy, low self esteem and poor concentration. Acupuncture has a long history of use in China and Japan. Traditional Chinese medicine theory describes a state of health maintained by a balance of energy in the body. Acupuncture involves the insertion of fine needles into different parts of the body to correct the imbalance of energy in the body. There are a range of styles of acupuncture from traditional/classical acupuncture, auricular

A therapy that uses dogs or other pets to improve the physical and mental health of patients with certain acute or chronic diseases. There is evidence from one systematic review that the introduction of animal assisted activities may have beneficial effects on the severity of depressive symptoms in older people resident in nursing homes and psychiatric institutions. The degree to which the benefits found are a result of animal contact or human contact with

acupuncture, trigger point acupuncture, and single point acupuncture.

the animal facilitator is unclear and requires further investigation.

examining the use of PUFAs as a stand-alone treatment of depression.

**Polyunsaturated fatty acids**

**s-adenosyl-L-methionine**

with tricyclic antidepressants.

be taken as supplements.

**Animal assisted therapy**

extracts are available as supplements.

**2.5 Complementary and alternative therapies**

**Chromium**

**Ginseng**

**Acupuncture**

Homeopathy A system of medicine which is based on treating the individual with highly diluted substances given mainly in tablet form, which trigger the body's natural system of healing.

#### **Light therapy**

Treatment that involves regular use of a certain spectrum of lights in a light panel or light screen that bathes the person in that light. Light therapy is also used to treat conditions such as seasonal affective disorder (seasonal depression).

#### **Massage therapy**

The manipulation of the soft tissues of the body - the muscles, tendons and ligaments. The therapeutic value of massage has been recorded in several studies. It has been shown to reduce stress and anxiety; relax muscles; aid in circulation, digestion, and excretion; and reduce pain perception. There are many different types of massage -- effleurage, deep tissue, and relaxation massage. Even the simplest massage may convey to the recipient a feeling of being cared for. Both maternal and infant massage have been evaluated in the treatment of postpartum depression.

#### **Aromatherapy**

A therapy based on the use of very concentrated "essential" oils from the flowers, leaves, bark, branches, rind or roots of plants with purported healing properties. Aromatherapy involves the administration of pure essential oils of fragrant plants either through breathing the aromatic vapours using an aroma diffuser, or absorbing diluted oils through the skin in a bath or during massage.

#### **Yoga**

An ancient system of breathing practices, physical exercises and postures, and meditation, intended to integrate the practitioner's body, mind, and spirit.

#### **Reiki**

A hands-on alternative healing technique that involves the exchange of energy between practitioner and patient to restore mental, physical, emotional, and spiritual balance.

#### **Reflexology**

Involves massage of reflex areas found in the feet and the hands.

#### **T'ai Chi**

A Chinese exercise system that uses slow, smooth, body movements to achieve a state of relaxation of both body and mind. Thought field therapy Involves tapping with the fingers at meridian points on the upper body and hands.

#### **3. Conclusion**

In the present review, a number of drug and non-drug strategies group setting may be considered as a treatment option to reduce relapse in patients with depression who have

Recent Therapies in Depression 355

[16] Simpson S, Corney R, Beecham J (2003). A randomized controlled trial to evaluate the

[18] Singh NA, Clements KM, Singh MA (2001). The efficacy of exercise as a long-term

[19] Nabkasorn C, Miyai N, Sootmongkol A, Junprasert S, Yamamoto H, Arita M, Miyashita

[20] Mather AS, Rodriguez C, Guthrie MF, McHarg AM, Reid IC, McMurdo ME (2002).

[25] Souter MA, Miller MD (2007). Do animal-assisted activities effectively treat

[26] Mukaino Y, Park J, White A, Ernst E (2005). The effectiveness of acupuncture for

[27] Pilkington K, Kirkwood G, Rampes H, Fisher P, Richardson J (2005).Homeopathy for

[28] Even C, Schroder CM, Friedman S, Rouillon F (2008). Efficacy of light therapy in nonseasonal depression: A systematic review. J. Affect. Disord., 108: 11-23. [29] Hou WH, Chiang PT, Hsu TY, Chiu SY, Yen YC (2010). Treatment effects of massage therapy in depressed people: a meta-analysis. J. Clin. Psychiatry, 71: 894-901. [30] van der Watt G, Janca A (2008). Aromatherapy in nursing and mental health

[31] Pilkington K, Kirkwood G, Rampes H, Richardson J (2005). Yoga for depression: The

[32] Lee MS, Pittler MH, Ernst E (2008). Effects of Reiki in clinical practice: a systematic

[33] Ernst E (2009). Is reflexology an effective intervention? A systematic review of

review of randomized clinical trials. Int. J. Clin. Pract., 62: 947-954.

randomised controlled trials. Med. J. Aust., 191: 263-266.

depression - A systematic review of randomized controlled trials. Acupunct. Med.,

depression: a systematic review of the research evidence. Homeopathy, 94: 153-163.

depression?A meta-analysis. Anthrozoos, 20: 167-180.

practice patients with chronic depression. Psychol. Med., 33: 229-239. [17] Watt LM, Cappeliez P (2000). Integrative and instrumental reminiscence therapies for

effectiveness.Aging Ment. Health, 4: 166-177.

symptoms. Eur. J. Public Health, 16: 179-184.

Biol. Sci. Med. Sci., 56: 497-504.

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care.Contemp. Nurse., 30: 69-75.

research evidence. J. Affect. Disord., 89: 13-24.

23: 70-76.

effectiveness and cost-effectiveness of psychodynamic counselling for general

depression in older adults: Intervention strategies and treatment

antidepressant in elderly subjects: a randomized, controlled trial. J. Gerontol. A

K (2006). Effects of physical exercise on depression, neuroendocrine stress hormones and physiological fitness in adolescent females with depressive

Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomized controlled trial. Br. J. Psychiatry, 180: 411-415. [21] Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO (2005). Exercise treatment for depression: efficacy and dose response. Am. J. Prev. Med., 28: 1-8. [22] Waite LW, Holder MD (2003). Assessment of the Emotional Freedom Technique: An Alternative Treatment for Fear. Sci. Rev. Mental Health Pract., 2: 20-26. [23] Leo RJ, Ligot Jr JSA (2007). A systematic review of randomized controlled trials of acupuncture in the treatment of depression. J. Affect. Disord., 97: 13-22. [24] Smith CA (2005). Acupuncture for depression (Cochrane Review). In: Cochrane Library,

had three or more episodes. Whereas, problem solving therapy and short term psychodynamic psychotherapy may be considered as a treatment option in depressed patients. Structured exercise may be considered as a treatment option for patients with depression. No applicable evidences were identified on which to base a recommendation for complementary and alternative therapies.

#### **4. References**

had three or more episodes. Whereas, problem solving therapy and short term psychodynamic psychotherapy may be considered as a treatment option in depressed patients. Structured exercise may be considered as a treatment option for patients with depression. No applicable evidences were identified on which to base a recommendation for

[1] Bedi N, Chilvers C, Churchill R, Dewey M, Duggan C, Fielding K, Gretton V, Miller P,

[2] Alisa W (2008). Neurolinguistic psychotherapy: A postmodern Alladin A, Alibhai A

[3] Dimidjian S, Davis KJ (2009). Newer variations of cognitive-behavioral therapy:

[4] Cuijpers P, van Straten A, Warmerdam L (2007). Behavioral activation treatments of

[6] Hensley PL, Nadiga D, Uhlenhuth EH (2004). Long-term effectiveness of cognitive

[7] Klausner EJ, Clarkin JF, Spielman L, Pupo C, Abrams R, Alexopoulos GS (1998). Late life

[8] Leichsenring F (2001). Comparative effects of short-term psychodynamic psychotherapy

[9] Michael B, Gillian EH (2001). Counselling and interpersonal therapies for depression:

[10] Luty SE, Carter JD, McKenzie JM, Rae AM, Frampton CMA, Mulder RT, Joyce PR

[11] Barbato A, D'Avazo B (2007). Marital therapy for depression (Cochrane Review). In:

[12] Allison S, Stacey K, Dadds V, Roeger L, Wood A, Martin G (2003). What the family brings: gathering evidence for strengths-based work. J. Fam. Ther., 25: 263-284. [13] de Mello MF, de Jesus Mari J, Bacaltchuk J, Verdeli H, Neugebauer R (2005). A

depressive disorders. Eur. Arch. Psychiatry Clin. Neurosci., 255: 75-82. [14] Maratos AS, Gold C, Wang X, Crawford MJ (2008). Music therapy for depression

[15] Cuijpers P, van Straten A, Warmerdam L (2007). Problem solving therapies for

(Cochrane Review). In: The Cochrane Library, London: Wiley, p. 1.

depression: A meta-analysis. Eur. Psychiatry, 22: 9-15.

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behavioural therapy for depression. Br. J. Psychiatry, 190: 496-502.

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(2007). Cognitive hypnotherapy for depression: An empirical investigation. Int. J.

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Rep., 11: 453-458.

**4. References**

**15**

*Brazil*

**Deep Brain Stimulation for**

**A State-of-the-Art Review**

Lucas Crociati Meguins *Section of Neurosurgery,*

*Department of Neurological Sciences, Hospital de Base da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo*

**Treatment-Resistant Depression:**

Depression is a common underdiagnosed, undertreated and costly mood disorder associated with substantial morbidity and mortality (1-3). It is related to the emotion of sadness or irritability and accompanied by several psycophysiological changes, such as disturbances in sleep, appetite or sexual desire; constipation; loss of the ability to experience pleasure in work or with friends; crying; suicidal thoughts; and slowing of speech and action (4-6). Approximately 5% of the population has major depression at any given time,

Depressive mood is one of the most common – and potentially dangerous – psychiatric complications of every chronic disease because it often worsens the overall clinical condition. The prevalence of depression in patients with chronic conditions ranges from 25 to 33 percent and is frequent among people hospitalized with cancer, who have had a recent heart attack or stroke, or have diabetes or Parkinson's disease (7). Besides, even between non-hospitalized patients, depression has an important effect on life and may limit the social activities of individuals. People who are depressed tend to be more withdrawn from their community, friends and family, are less likely to work, present a decreased productivity and retire earlier. The relevant social-economic and clinical impacts of mood disorder, especially depression, on patient's life have drawn attention to possible therapeutic mechanisms that could improve the quality of life and outcomes of

The clinical approach of patients suffering of depressive mood has evolved considerably throughout years and includes mainly supportive care combined with pharmacotherapy and psychotherapy (8, 9). Globally, treatment planning requires coordination of short-term strategies to induce remission associated with longer term maintenance designed to prevent recurrence. The wide variety of drugs available to treat depressive patients has given the

physician a large spectrum of therapeutic possibilities for a rationale approach.

with men experiencing a lifetime risk of 7%-12%; and women 20%-25% (3, 5).

**1. Introduction**

depressive patients.

[34] Wang C, Bannuru R, Ramel J, Kupelnick B, Scott T, Schmid CH (2010). Tai Chi on psychological well-being: systematic review and metaanalysis. BMC Complement. Altern. Med., 10: 23.

## **Deep Brain Stimulation for Treatment-Resistant Depression: A State-of-the-Art Review**

#### Lucas Crociati Meguins

*Section of Neurosurgery, Department of Neurological Sciences, Hospital de Base da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo Brazil*

#### **1. Introduction**

356 Clinical, Research and Treatment Approaches to Affective Disorders

[34] Wang C, Bannuru R, Ramel J, Kupelnick B, Scott T, Schmid CH (2010). Tai Chi on

Altern. Med., 10: 23.

psychological well-being: systematic review and metaanalysis. BMC Complement.

Depression is a common underdiagnosed, undertreated and costly mood disorder associated with substantial morbidity and mortality (1-3). It is related to the emotion of sadness or irritability and accompanied by several psycophysiological changes, such as disturbances in sleep, appetite or sexual desire; constipation; loss of the ability to experience pleasure in work or with friends; crying; suicidal thoughts; and slowing of speech and action (4-6). Approximately 5% of the population has major depression at any given time, with men experiencing a lifetime risk of 7%-12%; and women 20%-25% (3, 5).

Depressive mood is one of the most common – and potentially dangerous – psychiatric complications of every chronic disease because it often worsens the overall clinical condition. The prevalence of depression in patients with chronic conditions ranges from 25 to 33 percent and is frequent among people hospitalized with cancer, who have had a recent heart attack or stroke, or have diabetes or Parkinson's disease (7). Besides, even between non-hospitalized patients, depression has an important effect on life and may limit the social activities of individuals. People who are depressed tend to be more withdrawn from their community, friends and family, are less likely to work, present a decreased productivity and retire earlier. The relevant social-economic and clinical impacts of mood disorder, especially depression, on patient's life have drawn attention to possible therapeutic mechanisms that could improve the quality of life and outcomes of depressive patients.

The clinical approach of patients suffering of depressive mood has evolved considerably throughout years and includes mainly supportive care combined with pharmacotherapy and psychotherapy (8, 9). Globally, treatment planning requires coordination of short-term strategies to induce remission associated with longer term maintenance designed to prevent recurrence. The wide variety of drugs available to treat depressive patients has given the physician a large spectrum of therapeutic possibilities for a rationale approach.

Deep Brain Stimulation for Treatment-Resistant Depression: A State-of-the-Art Review 359

reported that the subgenual cingulated region (Brodman area 25) is a potential target to electrical stimulation with effective reverse of symptoms in patients suffering treatmentresistant depression, a large number of studies have been conduced to explore other potential sites in the brain that could be involved on the mechanisms of depressive mood

This procedure is characterized by a stereotactical implantation of an intracranial electrode that is connected to a pulse generator/battery pack (26). In 1947, at Temple University in Philadelphia, the neurologist Spiegel and the neurosurgeon Wycis first described a stereotactic apparatus and its use in humans to perform ablative procedures (27). The great knowledge achieved from the treatment of patients with movement disorders with DBS, such as Parkinson's disease, primary dystonia, and essential tremor, allowed its experimental use also on patients with treatment-resistant depression with encouraging results. Due to its reversible, revisable and adjustable potential, DBS represents an alternative and additional therapeutic approach to treatment-resistant

The initial evidence that a focal disrupting pathological activity in limbic-cortical pathways was present in patients with negative mood was observed by Mayberg and colleagues, in 1999 (28). Using functional neuroimaging studies, they consistently demonstrated the involvement of the subgenual cingulate (Cg25) (Brodmann area 25) in both the acute sadness and antidepressant treatment effects. A markedly increased blood flow was noted to the Cg25 during induction of transient normal sadness and, in contrast, a decreased activity was reported with clinical response to different antidepressant treatments, which suggested a critical role for this region in modulating negative mood states. This scientific observation raised the hypothesis that a therapeutic intervention on specific sites of the limbic-cortical circuits could effectively reverse the symptoms of otherwise treatmentresistant depression. Mayberg and colleagues, in 2005 (29), on an open-label study, applied bilateral DBS on the subcallosal cingulate white matter in six patients with treatmentresistant depression and observed a clinically significant antidepressant response in four after 6 months, which is known as the first published report of DBS for treatment-resistant

Based on the presence of neuronal dysregulation in limbic-cortical circuits and positive lesional effects, various target areas for depressive disorders have been discussed. Schlaepfer and colleagues, in 2008 (30), stimulating the nucleus accumbens of 3 patients, observed after one week, 42% reduction in symptoms. Malone and colleagues, in 2009 (31), stimulating the ventral internal capsule and ventral striatum of 15 patients, noted a distinct reduction in symptoms by 57% during 12 months. Lozano and colleagues, in 2008 (32), stimulating the subgenual area of cingulum of 20 patients, observed reduction in symptoms by an average 48% during 12 months, with 2 non-responders and 7 remission. Other targets for DBS in treatment resistant depression have been proposed, including globus pallidus internus, inferior thalamic peduncle, lateral habenula and the rostral cingulated cortex (33,

The ideal patient that may benefit from DBS is still a matter of controversy. The failure to two antidepressant treatments in the current episode appears to have a predictive validity. In STAR\*D, remission rates in successive stages of treatment were 36.8% in the first treatment, 30.6% in the second treatment, 13.7% in the third treatment, and 13.0% in

disorders.

depression.

depression.

34) (Table 1).

Approximately 35 million adults in Unite States population, at least once in lifetime, experience an episode of major depression (3). The essential feature of a major depressive event is defined as a persistent period of at least two weeks in which there is either depressive mood or the loss of interest or pleasure in nearly all activities (DSM-IV). The available treatment currently used includes selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA), selective norepinephrine reuptake inhibitors (NRI) and monoamine oxidase inhibitors (MAOI). However, only 47% of patients respond well to antidepressant treatment and only 33% of patients achieve remission in the first line of treatment with a widely used selective serotonin reuptake inhibitors (10). Additionally, relapse within 6-12 months is verified in approximately 50% of those who remit (11). Therefore, while currently available treatments are amongst the most widely prescribed drugs, they fail to have an effect on many patients and have incomplete effects for many others. Treatment-resistant depression has an estimated prevalence of 2-5% and continued depressive symptoms are directly responsible to ongoing functional impairment, increased utilization of health care resources, a high risk of suicide and an overall increased mortality (12-14). An effective treatment is then necessary, but there is very limited evidence for the efficacy of any specific therapeutic intervention in chronic, treatment-refractory depression.

Electroconvulsive therapy (ECT) is the main procedure indicated to patients resistant to antidepressive medications and consists of the induction of convulsive crises by means of applying an electric current through the brain for therapeutic purpose (15). The remission rate is of depression with electroconvulsive therapy varies, generally, from 50% to 80% (15). However, ECT may have important side effects, especially cognitive impairment, that can limit its clinical use (16) and it is associated with a high relapse rate (15, 17).

Repetitive transcranial magnetic stimulation (rTMS) was recently approved by FDA (Food and Drug Administration) for the treatment of depression that has not responded to one antidepressant medication. This procedure is well-tolerated and has few side effects. Its mechanism of therapeutic action is linked to the principal of electromagnetic induction discovered by Faraday in 1831 by wich electrical energy and magnetic fields are related. According to Pascual-Leone, an increased neuronal excitability linked to the increase of magnetic field may produce electrical currents in certain areas of the brain, especially the left prefrontal cortex, and reduce the depressive symptoms (18). rTMS has been described as a generally safe technique with consistent statistically significant antidepressant results (19, 20), however is associated with relatively low response rate and the maintenance of benefits over time is relatively unknown (21).

Vagus nerve stimulation (VNS) was approved in 2005 for the treatment of patients failing to respond to, at least, four antidepressant drugs and refers to electrical stimulation of the cervical portion of the left vagus nerve through a surgically implanted electrode and pulse generator. Surgical risks are relatively minor and long-term treatment is usually well tolerated. However, it has been noted that only a substantial minority of patients with extremely difficult-to-treat depressive disorder benefit from VNS and 21%-50% of patients who responded to VNS failed to maintain at least a 40% decrease in baseline depression severity over 1-2 years (22-24).

Deep brain stimulation (DBS) has been described as a promising therapy to severe and treatment-resistant depression. Since 2005, when Mayberg and colleagues (25) have

Approximately 35 million adults in Unite States population, at least once in lifetime, experience an episode of major depression (3). The essential feature of a major depressive event is defined as a persistent period of at least two weeks in which there is either depressive mood or the loss of interest or pleasure in nearly all activities (DSM-IV). The available treatment currently used includes selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA), selective norepinephrine reuptake inhibitors (NRI) and monoamine oxidase inhibitors (MAOI). However, only 47% of patients respond well to antidepressant treatment and only 33% of patients achieve remission in the first line of treatment with a widely used selective serotonin reuptake inhibitors (10). Additionally, relapse within 6-12 months is verified in approximately 50% of those who remit (11). Therefore, while currently available treatments are amongst the most widely prescribed drugs, they fail to have an effect on many patients and have incomplete effects for many others. Treatment-resistant depression has an estimated prevalence of 2-5% and continued depressive symptoms are directly responsible to ongoing functional impairment, increased utilization of health care resources, a high risk of suicide and an overall increased mortality (12-14). An effective treatment is then necessary, but there is very limited evidence for the efficacy of any specific therapeutic intervention in chronic,

Electroconvulsive therapy (ECT) is the main procedure indicated to patients resistant to antidepressive medications and consists of the induction of convulsive crises by means of applying an electric current through the brain for therapeutic purpose (15). The remission rate is of depression with electroconvulsive therapy varies, generally, from 50% to 80% (15). However, ECT may have important side effects, especially cognitive impairment, that can

Repetitive transcranial magnetic stimulation (rTMS) was recently approved by FDA (Food and Drug Administration) for the treatment of depression that has not responded to one antidepressant medication. This procedure is well-tolerated and has few side effects. Its mechanism of therapeutic action is linked to the principal of electromagnetic induction discovered by Faraday in 1831 by wich electrical energy and magnetic fields are related. According to Pascual-Leone, an increased neuronal excitability linked to the increase of magnetic field may produce electrical currents in certain areas of the brain, especially the left prefrontal cortex, and reduce the depressive symptoms (18). rTMS has been described as a generally safe technique with consistent statistically significant antidepressant results (19, 20), however is associated with relatively low response rate and the maintenance of benefits

Vagus nerve stimulation (VNS) was approved in 2005 for the treatment of patients failing to respond to, at least, four antidepressant drugs and refers to electrical stimulation of the cervical portion of the left vagus nerve through a surgically implanted electrode and pulse generator. Surgical risks are relatively minor and long-term treatment is usually well tolerated. However, it has been noted that only a substantial minority of patients with extremely difficult-to-treat depressive disorder benefit from VNS and 21%-50% of patients who responded to VNS failed to maintain at least a 40% decrease in baseline depression

Deep brain stimulation (DBS) has been described as a promising therapy to severe and treatment-resistant depression. Since 2005, when Mayberg and colleagues (25) have

limit its clinical use (16) and it is associated with a high relapse rate (15, 17).

treatment-refractory depression.

over time is relatively unknown (21).

severity over 1-2 years (22-24).

reported that the subgenual cingulated region (Brodman area 25) is a potential target to electrical stimulation with effective reverse of symptoms in patients suffering treatmentresistant depression, a large number of studies have been conduced to explore other potential sites in the brain that could be involved on the mechanisms of depressive mood disorders.

This procedure is characterized by a stereotactical implantation of an intracranial electrode that is connected to a pulse generator/battery pack (26). In 1947, at Temple University in Philadelphia, the neurologist Spiegel and the neurosurgeon Wycis first described a stereotactic apparatus and its use in humans to perform ablative procedures (27). The great knowledge achieved from the treatment of patients with movement disorders with DBS, such as Parkinson's disease, primary dystonia, and essential tremor, allowed its experimental use also on patients with treatment-resistant depression with encouraging results. Due to its reversible, revisable and adjustable potential, DBS represents an alternative and additional therapeutic approach to treatment-resistant depression.

The initial evidence that a focal disrupting pathological activity in limbic-cortical pathways was present in patients with negative mood was observed by Mayberg and colleagues, in 1999 (28). Using functional neuroimaging studies, they consistently demonstrated the involvement of the subgenual cingulate (Cg25) (Brodmann area 25) in both the acute sadness and antidepressant treatment effects. A markedly increased blood flow was noted to the Cg25 during induction of transient normal sadness and, in contrast, a decreased activity was reported with clinical response to different antidepressant treatments, which suggested a critical role for this region in modulating negative mood states. This scientific observation raised the hypothesis that a therapeutic intervention on specific sites of the limbic-cortical circuits could effectively reverse the symptoms of otherwise treatmentresistant depression. Mayberg and colleagues, in 2005 (29), on an open-label study, applied bilateral DBS on the subcallosal cingulate white matter in six patients with treatmentresistant depression and observed a clinically significant antidepressant response in four after 6 months, which is known as the first published report of DBS for treatment-resistant depression.

Based on the presence of neuronal dysregulation in limbic-cortical circuits and positive lesional effects, various target areas for depressive disorders have been discussed. Schlaepfer and colleagues, in 2008 (30), stimulating the nucleus accumbens of 3 patients, observed after one week, 42% reduction in symptoms. Malone and colleagues, in 2009 (31), stimulating the ventral internal capsule and ventral striatum of 15 patients, noted a distinct reduction in symptoms by 57% during 12 months. Lozano and colleagues, in 2008 (32), stimulating the subgenual area of cingulum of 20 patients, observed reduction in symptoms by an average 48% during 12 months, with 2 non-responders and 7 remission. Other targets for DBS in treatment resistant depression have been proposed, including globus pallidus internus, inferior thalamic peduncle, lateral habenula and the rostral cingulated cortex (33, 34) (Table 1).

The ideal patient that may benefit from DBS is still a matter of controversy. The failure to two antidepressant treatments in the current episode appears to have a predictive validity. In STAR\*D, remission rates in successive stages of treatment were 36.8% in the first treatment, 30.6% in the second treatment, 13.7% in the third treatment, and 13.0% in

Deep Brain Stimulation for Treatment-Resistant Depression: A State-of-the-Art Review 361

the best adjunctive therapy, the potential interactions of pharmacotherapy and the relative

This review aimed to describe the context in which DBS has emerged as an experimental therapy for refractory depression, present a brief historical note, discuss the different targets in these pathological neuro-psychiatric disorder, review the preliminary results of some clinical studies, and discuss the pros and cons of the method, as well as the possible adverse

The author appreciates the remarkable contribution made by Dr. Antônio Ronaldo Spotti, Dr. Carlos Eduardo Dall'aglio Rocha, and Dr. Fábio de Nazaré Oliveira, all from the Department of Neurological Sciences, Hospital de Base da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil, reviewing the

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**2. Acknowledgment**

chapter.

**3. References**

Table 1. deep brain stimulation in patients presenting treatment-resistant depression.

the forth treatment (11). Additionally, the likelihood of remission is markedly lower for patients for whom two or more adequate antidepressant trials failed (11). Therefore, in some studies, to qualify for DBS, patients had to be in an episode of major depression for at least 1 year and had to have failed to respond to at least four treatments (32). Exclusion criteria usually includes substance abuse, severe personality disorder and psychotic depression (35).

The potential for adverse effects from DBS for treatment-resistant depression has not been completely studied. Lozano and colleagues, in 2008 (32), reported increased depression in 10% of patients that underwent DBS of the subgenual area of cingulum. Moreover, Malone and colleagues, in 2009 (31), describe hippomanic episodes, increased suicidility and syncope on patients submitted to DBS of internal capsule/ventral striatum. Future studies must carefully point the most commons adverse effects and complications, and the specific targets related to it as well.

DBS is a recently proposed therapeutic approach to treatment-resistant depression and, therefore, remains with many unsolved questions. Future investigations must correctly address which patient benefits most from the surgical procedure and which is the best therapeutic target or, if not possible, which target best correlates to specific symptoms of depression. Large, randomized placebo-controlled studies of DBS for treatment-resistant are necessary to describe the potential risks and complications from operation. Additionally, as the study of DBS progresses, complementary information must put into evidence which is the best adjunctive therapy, the potential interactions of pharmacotherapy and the relative safety and efficacy of the various DBS targets.

This review aimed to describe the context in which DBS has emerged as an experimental therapy for refractory depression, present a brief historical note, discuss the different targets in these pathological neuro-psychiatric disorder, review the preliminary results of some clinical studies, and discuss the pros and cons of the method, as well as the possible adverse effects and future perspectives.

#### **2. Acknowledgment**

360 Clinical, Research and Treatment Approaches to Affective Disorders

**SITE**

cingulum

accumbens

cingulum

capsule/ventral striatum

cingulum

cingulate gyrus

Spain 8 Subgenual area of

**SYMPTOMS REDUCTION**

71%

42%

48%

57%

50%

64.3%

**YEAR REFERENCE PLACE PATIENTS STIMULATION**

**2005** Mayberg *et al* (28) Canada 6 Subgenual area of

**2008** Lozano *et al* (31) Canada 20 Subgenual area of

**2009** Malone *et al* (30) USA 15 ventral internal

**2011** Kennedy *et al* (36) Canada 20 Subcallosal

Table 1. deep brain stimulation in patients presenting treatment-resistant depression.

the forth treatment (11). Additionally, the likelihood of remission is markedly lower for patients for whom two or more adequate antidepressant trials failed (11). Therefore, in some studies, to qualify for DBS, patients had to be in an episode of major depression for at least 1 year and had to have failed to respond to at least four treatments (32). Exclusion criteria usually includes substance abuse, severe personality disorder and psychotic

The potential for adverse effects from DBS for treatment-resistant depression has not been completely studied. Lozano and colleagues, in 2008 (32), reported increased depression in 10% of patients that underwent DBS of the subgenual area of cingulum. Moreover, Malone and colleagues, in 2009 (31), describe hippomanic episodes, increased suicidility and syncope on patients submitted to DBS of internal capsule/ventral striatum. Future studies must carefully point the most commons adverse effects and complications, and the specific

DBS is a recently proposed therapeutic approach to treatment-resistant depression and, therefore, remains with many unsolved questions. Future investigations must correctly address which patient benefits most from the surgical procedure and which is the best therapeutic target or, if not possible, which target best correlates to specific symptoms of depression. Large, randomized placebo-controlled studies of DBS for treatment-resistant are necessary to describe the potential risks and complications from operation. Additionally, as the study of DBS progresses, complementary information must put into evidence which is

**2011** Puigdemont *et al*

depression (35).

targets related to it as well.

(35)

**2008** Schlaepfer *et al* (29) Germany 3 Nucleus

The author appreciates the remarkable contribution made by Dr. Antônio Ronaldo Spotti, Dr. Carlos Eduardo Dall'aglio Rocha, and Dr. Fábio de Nazaré Oliveira, all from the Department of Neurological Sciences, Hospital de Base da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil, reviewing the chapter.

#### **3.

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AM. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to

### *Edited by Mario Francisco Juruena*

The causes, development and outcomes of disorders are determined by the relationship of psychological, social and cultural factors with biochemistry and physiology. Biochemistry and physiology are not disconnected and different from the rest of our experiences and life events. This system is based on current studies that report that the brain and its cognitive processes show a fantastic synchronization. Written by the foremost experts on Affective Disorders worldwide, this book is characterized by its innovative, refreshing, and highly sensitive perspective on current knowledge of diagnostic, neurobiology, early life stress and treatment of Mood Disorders. The authors share a deep understanding of unique challenges and difficulties involved in Affective Disorders, and have achieved a balance among clinical, research and new treatment approaches to Affective Disorders. The chapters are written in a comprehensive, easily readable, and highly accessible style, stimulating readers, clinicians and researchers.

Photo by josé amorim / iStock

Clinical, Research and Treatment Approaches to Affective Disorders

Clinical, Research and

Treatment Approaches to

Affective Disorders

*Edited by Mario Francisco Juruena*


**7. Conclusion**

*Practical Applications of Laser Ablation*

**80**

**Figure 22.**

**Figure 21.**

*Schematic of laser texturing process.*

consumables like steel grits and acid to texture surfaces. Unlike those treatments, the laser texturing process functions without consumables. This results in low operating costs, low maintenance, and improved health and safety in the workplace.

*Schematic of laser surface texture dimensions: (a) circle, (b) oval.*

The new materials have been developed every day to meet the demand of competitive situations. The surface properties of substrate can be improved by a number of methods such as laser surface alterations such as surface hardening, melting, alloying, cladding and texturing in order to improve the mechanical performance and tribological behavior. In this work, the effect of laser process parameters on microstructure, hardness and wear rate of materials have been presented. The laser surface hardening is needed to high stressed components namely gear teeth, gears, shafts, camshafts, axles, cylinder liners and exhaust valves. The laser surface melting can be adopted in biomedical alloys, sport cars and power plants made of stainless steel, magnesium alloy and superalloys. The locomotive, aerospace and structural components made of aluminum alloys, titanium alloys and magnesium alloys have required the laser surface alloying to improve the surface properties of metals. The repaired and refurbishment components such as internal combustion engine parts, gas turbine, turbine blades and tools are highly needed the laser surface cladding to improve the surface properties of metals. The texturing on material is used to increase the tribological characteristics of materials resulting in improved surface roughness, wettability, improve load capacity, wear rates, lubricating lifetime and reduce friction coefficient. Hence, the laser based surface modification techniques can be adopted to improve the performance of the components.


*Proceeding Paper* **Geopolymers Based on Fly Ash from the Bełchatów Power Plant †**

**Agnieszka B ˛ak \* , Patrycja Bazan , Kinga Pławecka and Michał Łach**

Faculty of Material Engineering and Physics, Cracow University of Technology, Jana Pawła II 37, 31-864 Cracow, Poland

**\*** Correspondence<EMAIL_ADDRESS>
† Presented at the 10th MATBUD'2023 Scientific-Technical Conference "Building Materials Engineering and Innovative Sustainable Materials", Cracow, Poland, 19–21 April 2023.

**Abstract:** Geopolymer materials are attracting increasing interest from scientists due to their specific properties and the possibility of using waste materials from the power industry for their production. The most common raw material for their production is fly ash from the combustion of hard coal in pulverized coal boilers, but it is also possible to use ash from the combustion of lignite for this purpose. This article presents the results of a study of geopolymers produced with the use of ashes from lignite combustion at the Bełchatów Power Plant. It includes characterization of the ashes (laser particle size analysis, SEM/EDS morphology, XRD phase composition) and the strength properties of geopolymers made from these ashes and activated with 10 M and 14 M aqueous sodium hydroxide solution with water glass. As a result of this study, it was found that it is possible to obtain geopolymers characterized by flexural strength of almost 3 MPa and compressive strength of 30 MPa. A comparison of activators with concentrations of 10 M and 14 M made it possible to conclude that, due to the lack of significant differences in the properties of the obtained geopolymers, from an economic point of view, it is more advantageous in this case to use activators with a lower concentration.

**Keywords:** geopolymers; fly ash; fly ash from lignite; Belchatów; alkaline activation; flexural strength; compressive strength