does not affect them adversely Pupillary dilation occurs following use of many antidepressant drugs may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy Cerebrovascular adverse events (eg, stroke,transient ischemic attack), including fatalities, reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis; this drug combination is not approved for treatment of patients with dementia-related psychosis Olanzapine exhibits in vitro muscarinic receptor affinity; in premarketing clinical studies, this drug combination was associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism; such adverse reactions were not often the basis for study discontinuations; this drug combination should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, a history of paralytic ileus, or related condition Potential for abnormal bleeding with concomitant ASA, NSAIDs, or other antiplatelet drugs; case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and occurrence of gastrointestinal bleeding; bleeding reactions related to SNRIs and SSRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages; patients should be cautioned about risk of bleeding associated with concomitant use of this combination drug and NSAIDs, aspirin, or other drugs that affect coagulation Risk of mydriasis; may trigger angle closure attack in patients with angle-closure glaucoma with anatomically narrow angles without a patent iridectomy Therapy may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during initial dose-titration period; treatment should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, or conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medication Clinical worsening and suicide ideation may occur despite medication; consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms; if the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms Drug reaction with eosinophilia and systemic symptoms (DRESS) reported with olanzapine exposure; DRESS may present with a cutaneous reaction (eg, rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis; discontinue treatment if DRESS is suspected May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; for patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long- term antipsychotic therapy Seizures occurred in 0.2% fluoxetine/olanzapine-treated patients during open-label clinical studies; this drug combination should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold, eg, Alzheimer’s dementia; this drug combination is not approved for treatment of patients with Alzheimer’s disease; conditions that lower seizure threshold may be more prevalent in a population of ≥65 years of age Esophageal dysmotility and aspiration associated with antipsychotic drug use; aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer’s disease Disruption of body’s ability to reduce core body temperature has been attributed to antipsychotic drugs; appropriate care is advised when prescribing this drug combination for patients who will be experiencing conditions that may contribute to an elevation in core body temperature (eg, exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration Because of long elimination half-lives of fluoxetine and its major active metabolite, changes in dose will not be fully reflected in plasma for several weeks, affecting both strategies for titration to final dose and withdrawal from treatment; this is of potential consequence when drug discontinuation is required or when drugs are prescribed that might interact with fluoxetine and norfluoxetine following the discontinuation of fluoxetine Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) reported in association with administration of antipsychotic drugs (eg, olanzapine); clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia); additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure The diagnostic evaluation of patients with this syndrome is complicated; in arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS); other important considerations in differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology The management of NMS should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems for which specific treatments are available; there is no general agreement about specific pharmacological treatment regimens for NMS If after recovering from NMS, a patient requires treatment with an antipsychotic, the patient should be carefully monitored, since recurrences of NMS have been reported Allergic reactions Since the introduction of fluoxetine, systemic reactions, possibly related to vasculitis, have developed in patients with rash; although these reactions are rare, they may be serious, involving the lung, kidney, or liver; death has been reported to occur in association with these systemic reactions Anaphylactoid reactions, including bronchospasm, angioedema, and urticaria alone and in combination, reported Pulmonary reactions, including inflammatory processes of varying histopathology and/or fibrosis, reported rarely; these reactions occurred with dyspnea as the only preceding symptom; whether these systemic reactions and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known Furthermore, a specific underlying immunologic basis for these reactions has not been identified; upon appearance of rash or of other possible allergic phenomena for which an alternative etiology cannot be identified, therapy should be discontinued Activation of mania/hypomania A major depressive episode may be initial presentation of bipolar disorder; it is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a manic episode in patients at risk for bipolar disorder Whether any of the symptoms described for clinical worsening and suicide risk represent such a conversion is unknown; however, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression; it should be noted that this drug combination is approved for acute treatment of depressive episodes associated with bipolar I disorder Because of cyclical nature of bipolar I disorder, patients should be monitored closely for development of symptoms of mania/hypomania during therapy Tardive dyskinesia A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs; although prevalence of syndrome appears to be highest among elderly, especially elderly women, impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome; whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown Risk of developing tardive dyskinesia and likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase; however, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is withdrawn; antipsychotic treatment itself, however, may suppress (or partially suppress) signs and symptoms of syndrome and thereby may possibly mask the underlying process; the effect that symptomatic suppression has upon long-term course of syndrome is unknown This drug combination should be prescribed in a manner that is most likely to minimize risk of tardive dyskinesia; if signs and symptoms of tardive dyskinesia appear in a patient receiving this drug combination, drug discontinuation should be considered; however, some patients may require treatment with this drug combination despite presence of syndrome; the need for continued treatment should be reassessed periodically Serotonin syndrome Development of potentially life-threatening serotonin syndrome reported with SNRIs and SSRIs, including this drug combination, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea); patients should be monitored for emergence of serotonin syndrome Concomitant use of this drug combination with MAOIs intended to treat psychiatric disorders is contraindicated; should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue; all reports with methylene blue that provided information on route of administration involved intravenous administration in dose range of 1 mg/kg to 8 mg/kg; no reports involved administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking this drug combination; therapy should be discontinued before initiating treatment with the MAOI If concomitant use of this drug combination with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamines, and St. John's Wort is clinically warranted, patients should be made aware of potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases Treatment with this drug combination and any concomitant serotonergic agents should be discontinued immediately if adverse events occur and supportive symptomatic treatment should be initiated Leukopenia, neutropenia, agranulocytosis In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia, and agranulocytosis have been reported temporally related to antipsychotic agents Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia; patients with history of clinically significant low WBC or drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during first few months of therapy and discontinuation of this drug combination should be considered at first sign of clinically significant decline in WBC in absence of other causative factors Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur; patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue and have their WBC followed until recovery Hyponatremia Hyponatremia reported during treatment with SNRIs and SSRIs, including fluoxetine and this drug combination; in many cases, this hyponatremia appears to be the result of syndrome of inappropriate antidiuretic hormone secret Elderly patients may be at greater risk of developing hyponatremia with SNRIs and SSRIs; also, patients taking diuretics or who are otherwise volume depleted may be at greater risk; discontinuation of this drug combination should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls; more severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death QT prolongation Post-marketing cases of QT interval prolongation and ventricular arrhythmia including Torsade de Pointes have been reported in patients treated with fluoxetine; therapy should be administered with caution in patients with congenital long QT syndrome; a previous history of QT prolongation; a family history of long QT syndrome or sudden cardiac