Platelet monoamine oxidase response to lithium treatment in psychiatric patients. A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Pharmacotherapy of impaired affect in recovering schizophrenic patients. Trials of lithium, chlorpromazine and amitriptyline in schizoaffective patients. A controlled study of lithium vs. chlorpromazine in acute schizophrenics. Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial. Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder. Lithium addition to neuroleptic treatment in chronic schizophrenia: a randomized, double-blind, placebo-controlled, cross-over study. Efficacy of lithium in schizophrenia. Lithium and chlorpromazine in psychotic inpatients. Comparative effects of lithium and chlorpromazine in the treatment of acute manic states. The Northwick Park "functional" psychosis study: diagnosis and treatment response. Lithium versus fluphenazine for prophylaxis in mainly schizophrenic schizo-affectives. Lithium carbonate in chronic schizophrenia--a brief trial of lithium carbonate added to neuroleptics for treatment of resistant schizophrenic patients. Combination of lithium carbonate and haloperidol in schizo-affective disorder: a controlled study. Adjunctive carbamazepine or lithium carbonate in therapy-resistant chronic schizophrenia. Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.
Platelet monoamine oxidase (MAO) activity was studied in bipolar and schizophrenic patients treated with lithium and was found to be increased as a nonspecific drug effect. Greater MAO increase in manic patients was correlated with lesser clinical improvement. There was no correlation of MAO activity with short-term outcome in schizophrenic patients. Change in MAO was not correlated with lithium dosage or plasma levels. Patients with baseline MAO values below the median had the largest activity increases. Platelet MAO might thus be characterized as a state variable, increased by lithium as a nonspecific pharmacologic effect, with the increase associated with poor clinical outcome in manic patients. Lithium combined with major tranquilizers was administered to 22 hospitalized chronic schizophrenic patients with minimal neurotoxicity or other side effects. Moreover, 10 of the patients benefited significantly with lithium as compared to placebo in terms of blind psychiatric and nursing ratings and nonblind clinical judgments of outcome. These results contrast with previous negative reports in the literature and the generally poor prognosis in chronic schizophrenic patients. The authors suggest that a trial combining lithium with psychotropic drugs is warranted in schizophrenic patients who do not respond satisfactorily to conventional treatment Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.
                In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.
                For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.
                Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature. Two drug trials in schizoaffective patients are reported. Nineteen "schizomanic" patients were treated for one month, on a double blind basis, with chlorpromazine or lithium and 41 "schizodepressive" patients with amitriptyline, chlorpromazine or both. In the schizodepressive patients there was a trend to a better response to chlorpromazine, but drug response generally was poor, only 20 per cent of patients recovering within the month. In the schizomanic patients lithium seemed as effective as chlorpromazine, which supports the view that these patients were suffering from a variant of mania. nan This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean +/- SD dose = 13.6 +/- 8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean +/- SD lithium level = 0.98 +/- 0.13 mEq/l). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone. The safety and tolerability of clozapine combined with lithium were investigated because of potential additive risks as well as frequent usage in clinical practice. Ten hospitalized schizophrenic and 10 schizoaffective patients receiving clozapine maintenance therapy with partial therapeutic response were studied in a randomized controlled trial. CGI and PANSS outcome ratings were employed and a cognitive battery was administered at baseline and after 4 weeks of lithium and placebo administration. Barnes and UKU side effect ratings and laboratory safety data were obtained. Combined lithium-clozapine treatment was well tolerated except for reversible neurotoxic reactions in two schizophrenic patients. Safety measures showed no significant variations, even during lithium toxicity. Total WBC and absolute granulocyte counts increased with lithium and declined with placebo. Schizoaffective patients improved with lithium on CGI and PANSS total and negative symptom scales and the cognitive measures, whereas schizophrenic patients did not. Lithium added to clozapine in treatment regimens for hospitalized, treatment-resistant, schizoaffective patients appears to afford potential benefit without harmful effects; for schizophrenic patients, however, it did not afford improvement but posed a risk of lithium toxicity. We studied the effect of lithium addition to neuroleptic treatment in chronic schizophrenia, for which contradictory results have been produced in previous studies. Twenty-one chronic schizophrenic inpatients received lithium in a study with randomized, double-blind, placebo-controlled, cross-over design consisting of 8 weeks each of treatment with lithium capsules and identical placebo capsules. The total Brief Psychiatric Rating Scale (BPRS) scores at week 8 of the lithium treatment were improved significantly compared with those at week 8 of the placebo treatment. Of the BPRS subscales, however, only anxiety-depression improved, whereas none of the subscales for anergia, thought disturbance, activation and hostile-suspiciousness improved. There was no significant difference between the total Scale for the Assessment of Negative Symptoms (SANS) scores at any time during lithium and placebo treatment. These results suggest that the addition of lithium to neuroleptic treatment improves anxiety-depression in chronic schizophrenia. 60 Schizophrenic patients were given LiCo(3)/Chlorpromazine for 4 weeks, in a double blind cross over study with two placebo crossovers of 1 week before and two weeks after active treatment. Several core schizophrenic features showed significant reduction in severity with lithium. However, CPZ treatment was superior in terms of improvement, as compared to the other group on MBPRS and CGIS. Target symptoms may be one situation, where lithium could be tried and these results are discussed. A sample of recently hospitalized psychotic patients was assigned to treatment with lithium or chlorpromazine in a double-blind drug trial. Several diagnostic systems were used to characterize the patients. No relationship was found, regardless of criterion system used, between diagnosis and differences in drug effectiveness; specifically, the presence of "schizophrenic" symptoms did not predict a poor response to lithium. Among patients with physical overactivity, those treated with lithium terminated earlier and had poorer outcome than those treated with chlorpromazine. In patients who were not overactive, the two drugs were equally effective, and chronically psychotic patients had poorer outcomes regardless of drug. Lithium may be an effective treatment for acutely psychotic patients who are not overactive. The use of a lithium trial as a diagnostic tool may be unwarranted. nan Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of "functional" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion. nan The value of lithium carbonate as an adjunctive treatment of resistant schizophrenia was tested in a 4-week clinical trial using a single-blind, randomized, consent design. Treatment and control groups were drawn from a population of detained patients in an English special (maximum security) hospital. The 2 groups were comparable in terms of age, sex, severity of symptoms, length of hospitalization and concurrent neuroleptic dosage. The addition of lithium carbonate to the treatment regimen did not result in symptomatic improvement in patients completing the treatment protocol. The ethical and practical difficulties raised by the trial are discussed. Lithium carbonate alone has been shown to be inferior to neuroleptics alone in the treatment of excited schizo-affective illness. However, in clinical practice, lithium carbonate and neuroleptics are often combined in this disorder. We report a double-blind five-week controlled trial of lithium carbonate plus haloperidol vs placebo plus haloperidol in the treatment of excited schizo-affective patients. Eighteen patients were studied in each treatment group. Modest but statistically significant differences in favor of lithium carbonate plus haloperidol were found by week 5, using the Brief Psychiatric Rating Scale. Lithium carbonate plus haloperidol was favored both for affective schizo-affectives and for schizophrenic schizo-affectives. Lithium carbonate benefit did not seem to be restricted to affective symptoms only. In the clinical treatment of acute schizo-affective illness, the modest benefits of added lithium carbonate must be weighed against the risks of the drug's toxicity. nan Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study.
                Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study.
                Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium.
                Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.
There is no randomised trial-based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but does justify further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.