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Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis

  • Jaap Wijkstra (a1), Jeroen Lijmer (a2), Ferdi J. Balk (a3), John R. Geddes (a4) and Willem A. Nolen (a5)...
Abstract
Background

The optimal pharmacological treatment of unipolar psychotic depression is uncertain.

Aims

To compare the clinical effectiveness of pharmacological treatments for patients with unipolar psychotic depression.

Method

Systematic review and meta-analysis of randomised controlled trials.

Results

Ten trials were included in the review. We found no evidence that the combination of an antidepressant with an antipsychotic is more effective than an antidepressant alone. This combination was statistically more effective than an antipsychotic alone.

Conclusions

Antidepressant mono-therapy and adding an antipsychotic if the patient does not respond, or starting with the combination of an antidepressant and an antipsychotic, both appear to be appropriate options for patients with unipolar psychotic depression. However, clinically the balance between risks and benefits may suggest the first option should be preferred for many patients. Starting with an antipsychotic alone appears to be inadequate.

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Copyright
Corresponding author
Dr J. Wijkstra, University Medical Centre Utrecht, HP B01.206, PO Box 85500, 3508 GA, Utrecht, The Netherlands. E-mail: j.wijkstra@azu.nl
Footnotes
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Declaration of interest

JW and WN. are currently conducting a randomised controlled trial in patients with unipolar psychotic depression, which is financially supported by Wyeth and Astra Zeneca. These organisations also financially supported the literature search for this review.

Footnotes
References
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The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis

  • Jaap Wijkstra (a1), Jeroen Lijmer (a2), Ferdi J. Balk (a3), John R. Geddes (a4) and Willem A. Nolen (a5)...
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eLetters

Psychotic depression and �multi-aminergic� treatment strategies

Peter K Gillman, Consultant
04 May 2006

Dr P K Gillman MRCPsych. Consultant, Pioneer Valley Private Hospital Mackay Qld AustraliaPO Bob 86 Bucasia 4750Tel: 61-7- 4942 1883Fax 61-7- 4942 8283

Declaration of interest None

The resurgence of the suggestion that neuroleptic drugs should be used for treatment of psychotic, or refractory, depression is important because of the potential for worsening the illness; i.e. by lowering dopamine when it may

need to be raised. A previous meta-analytic study (Parker, Roy, et al, 1992) found a significant effect size only for the superiority of ECT over TCAs,but not TCAs + neuroleptic over TCAs, or MAOIs. The Wijkstra et. al. study (2006) substantiates the case against the usefulness of neuroleptics in psychotic depression. However, neither study was able to distinguish between 5-HT and NA (SNRI), vs. mono-aminergic, treatment strategies. It is both curious and disappointing that more attempts have not been made to simultaneously augment multiple mono-amine pathways, for two reasons: 1) major depression probably involves changes in NA, 5HT and DA. 2) the SNRI clomipramine is of superior efficacy for severe depression (DUAG, 1986).

Any results which suggest the superiority of SNRI over mono-aminergic strategies, like standard TCAs (which increase NA, but affect 5HT and DA very little, except for clomipramine), are thus of considerable importance. See Gillman (2006) for an in depth analysis of the issue of which TCAs exhibit clinically relevant SNRI potency.

I therefore report my analysis of 21 consecutive cases of psychotic depression, treated using SNRI strategies. Nineteen of the 21 (90%) recovered fully without either neuroleptics or ECT. Only unequivocal clinical data indicating delusions were used to justify the diagnosis of psychotic

depression. All patients were adjudged to be fully recovered by virtue of the fact that they were able to leave hospital and resume their normal functioning and responsibilities without significant functional impairment or symptoms. All were treated, and all followed up for a minimum of 2 years, by the author and remained well: except those few patients who did not maintain the same

maximal dose throughout follow-up. All those showed signs of early relapse, but recovered on restitution of the maximal dose.

Ten (of 21) cases had had no previous treatment in the index episode. Two had received bilateral ECT in the index episode prior to referral ; 2 had

bilateral ECT given by the author. Of the total of 21, 15 received clomipramine alone, 3 tranylcypromine alone, 2 sertraline + nortriptyline, 1 ECT (recovered). Three of the 4 ECT cases relapsed rapidly, but all 3 remitted with drug treatment.

Prudic’s (1990) results showed that about 85% of psychotic depressives respond to ECT, but 60% relapse within 1 year: leading them to sum up: ‘The implication is that 20% of medication resistant patients respond (to ECT) and maintain gains for 1 year’. So, as Wijkstra et. al. note, the fact that ‘many clinicians assume that ECT is more effective than pharmacotherapy’ is especially unfortunate. I hope my experience will encourage others to try ‘multi-aminergic’ strategies including MAOIs and sertraline + nortriptyline.

Danish University Antidepressant Group (1986) Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group. Psychopharmacology, 90, 131-138.

Gillman, P. K. (2006) A Review of Serotonin Toxicity Data: Implications for the Mechanisms of Antidepressant Drug Action. Biological Psychiatry, [Feb 3; Epub ahead of print].

Parker, G., Roy, K., Hadzi-Pavlovic, D., et al (1992) Psychotic (delusional) Depression: a meta-analysis of Physical Treatments. Journal of Affective Disorders, 24, 17 -24.

Prudic, J., Sackeim, H. A. & Devanand, D. P. (1990) Medication Resistance & Clinical response to Electroconvulsive Therapy. Psychiatry Research, 31, 287-296.

Wijkstra, J., Lijmer, J., Balk, F. J., et al (2006) Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis. British Journal of Psychiatry, 188, 410-415.
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