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Saturday, November 17, 2007

Again Antipsychotics for Depression Ineffective

This time I want to discuss a case series: Clozapine in medication- and ECT resistant depressed inpatients.
I usually discuss peer reviewed articles about randomized controlled trials appearing in Core Clinical Journals usually mitigating the positive results of these trials like in a recent RCT with rTMS. This time I want to make an exception.

I want to discuss this case series for the following reasons:

  • The topic is the use of antipsychotics for depressed patients for which several trials with antidepressants and ECT failed to deliver a sufficient response.

  • The authors got it published as a letter to the editor in spite of negative results.

  • The editor and reviewers accepted it for publication in spite of the negative results.

  • I like the Journal of Clinical Psychopharmacology because of their excellent guidance and service with publishing important information in their Journal.

  • I am a opponent for the use of antipsychotics for psychotic depression and certainly for nonpsychotic depression

The authors conducted an open trial in ECT-resistant depressed inpatients. The wanted to investigate the effect of clozapine in these patients. Arguments for this trials were:

  • Clozapine is effective in psychotic patients resistant to typical neuroleptics

  • Clozapine is also beneficial as an add on therapy in ECT-resistant schizophrenic and schizoaffective patients.

  • Recent interest in the addition of atypical antipsychotics to treatment options for "difficult to treat unipolar or bipolar depression".

They planned to include 10 patients with pharmacotherapy treatment failure and insufficient response to ECT as measured by Hamilton Rating Scale for Depression.

The study was discontinued after the inclusion of 5 patients (2 men and 3 women, 2 with unipolar and 3 with bipolar disorder).

ECT was continued during the trial accept for 1 patient because of the patients refusal.

The study was stopped because of "severely disrupting side effects". In all cases except 1 the side effects were severely disrupting in 2 of these cases the side-effects were critical due to neutropenia and an influenza like syndrome. There was no significant reduction in severity of the depression after 4 weeks of treatment. After 8 weeks 2 patients could be classified as partial responders, after 12 weeks only one patient could be classified as responder but there was no remission obtained.

I hope this publication will be noticed not only for its results but also for the importance of the publication of negative outcome, and again I express my respect and appreciation for the authors and editor.

Additional treatment with Clozapine to ECT is not a promising strategy in ECT resistant depressed patients, putting it mildly.

Since Clozapine has serious side-effects it is usually reserved for third-line use for patients with therapy resistant positive symptoms. The rare but potentially lethal side effects of clozapine is agranulocytosis and myocarditis. Furthermore it may rarely lower seizure threshold, cause leukopenia, cause hepatic dysfunction, weight gain and be associated with type II diabetes. More common side effects are predominantly anticholinergic in nature, with dry mouth, sedation and constipation.

Safer use of clozapine requires weekly blood monitoring for around five months followed by four weekly testing thereafter. Echocardiograms are recommended every 6 months to exclude cardiac damage.

Blogging on Peer-Reviewed Research

Discussed article:
J Clin Psychopharmacol. 2007 Dec;27(6):715-717.

Clozapine in Medication- and Electroconvulsive Therapy-Resistant, Depressed
Inpatients: A Case Series.

Quante A, Zeugmann S, Bajbouj M, Anghelescu I.

PMID: 18004147

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