Table 1 Key Papers identified from the literature search

McElroy SL, Dessain EC, Pope HG Jr, Cole JO, Keck PE Jr, Frankenberg FR, Aizley HG, O'Brien S [1]

1991

Clozapine in the treatment of Psychotic mood disorders, schizoaffective disorder and schizophrenia.

Retrospective Chart analysis of patients with 39 schizophrenia, 25 schizoaffective disorder and 14 bipolar disorder with psychotic features

Clozapine was shown to be useful in the treatment of patients with schizoaffective disorder or psychotic mood disorder who are treatment resistant or intolerant of side effects.

There was no standardisation of treatment given prior to clozapine administration. There was no comparison group or long term follow up of patients.

Banov MD, Zarate CA Jr, Tohen M, Scialabba D, Wines JD Jr, Kolbrener M, Kim JW, Cole JO. [2]

1994

Clozapine therapy in refractory affective disorders: polarity predicts response in long-term follow up.

Retrospective Review of 193 Case Notes of 52 Bipolar Disorder, 81 schizoaffective disorder, 14 unipolar depression, 40 schizophrenia, and 6 other disorder.

Clozapine is an efficacious and well-tolerated therapy for refractory affective illness. Manic symptomatology predicts a more favourable response than depression.

Heterogeneous groups studied, not standardised for demographics, no comparison group for treatment with clozapine, no knowledge of prior treatment given.

Collaborative Working Group on Clinical Trial Evaluations.[3]

1998

Evaluating the usefulness of atypical antipsychotics in reducing suicidality in schizophrenic patients and their use in affective disorders

Review

Atypical antipsychotics may be used as an adjunctive medication or an alternative to mood stabilizers in patients with affective disorders

Not specific to clozapine and not evaluating controlled trials.

Suppes T, Webb A, Paul B, Carmody T, Kraemer H, Rush AJ.[4]

1999

Clinical Outcome in a Randomised 1 year trial of Clozapine versus treatment as usual for patients with treatment resistant illness and a history of mania

Prospective randomised trial 38 patients with schizoaffective disorder and bipolar disorder.

Showed that clozapine had independent mood stabilising properties.

Looks at heterogeneous population of Not specific to psychotic depression.

Ranjan R, Meltzer HY.[5]

1996

Acute and Long term Effectiveness of Clozapine in treatment -resistant psychotic depression

Case Series Only 3 cases studied.

In all 3 cases, clozapine treatment was associated with significant improvement in both affective and psychotic symptoms. Maintenance in remission was sustained over many years

Only 3 cases studied, there was no comparison group.

Zarate CA Jr, Tohen M, Baldessarini RJ.[6]

1995

Clozapine in Severe Mood Disorders.

Systematic Review

Clozapine appears to be effective and well tolerated in the short term and maintenance of severe or psychotic mood disorders.

Heterogeneous analysis of different trials including case series, retrospective analysis and open label trials. No double blind studies specific to the treatment with clozapine. Outcome measures varied according to the trial used.

Naber D, Holzbach R, Perro C, Hippius H.[7]

1992

Clinical Management of Clozapine Patients in Relation to Efficacay and Side-Effects.

Retrospective analysis of 644 medical charts, patients who were given clozapine after standard neuroleptic treatment had failed.

Efficacy of clozapine was satisfactory in 55–72% of patients with organic psychosis, mania, psychotic depression or Parkinson's disease.

Majority of patients had schizophrenia and schizoaffective disorder only 54 had psychotic depression. The study tended to focus on the side effect profile of clozapine in schizophrenia

Dassa D, Kaladjian A, Azorin JM, Giudicelli S.[8]

1993

Clozapine in the Treatment of Psychotic Refractory Depression.

Case Study

Depressive and psychotic features improved after the administration of clozapine suggesting that clozapine could be efficient in psychotic refractory depression

Only one case studied.