Therapies — 14 March 2013

Atypical antipsychotics can help alleviate major depression when antidepressants fail, but at a heavy cost of side effects, research finds.

When used as adjunctive therapy, atypicals deliver a significant, albeit “small-to-moderate”, impact on depression symptom severity compared to placebo, a comprehensive new meta-analysis has concluded.

Around nine patients need to be treated for one to display a clinical response, and around ten for one to experience remission, the authors concluded.

However adverse effects were extremely common across the class, notably weight gain, sedation, restless leg syndrome and metabolic disturbances. Nor did the improvement in symptoms translate into any clear benefit on quality of life or functional impairment measures.

“Taken together, our metaanalysis found evidence of some improvement in clinician-assessed depressive symptoms, little evidence of substantial benefit in overall well-being, and abundant evidence of potential treatmentrelated harm,” US researchers wrote in PLOS Medicine.

The paper included 14 short-term trials, some previously unpublished, of atypical antipsychotics added to antidepressants for treating acutephase major depressive disorder in 3,500 patients. It did not specifically address the role of psychotic features within depression.

Atypical antipsychotics are not PBS listed for unipolar depression but off-label prescribing is thought to be common, said Professor Philip Mitchell, head of psychiatry at the University of NSW.

“There’s a lot of interest in this whole question of augmenting antidepressants with antipsychotics so this is very timely. It confirms the efficacy … but it becomes a balance against side effects,” he said.

Professor Mitchell stressed that antipsychotics were just one of many options when a firstchoice antidepressant failed.

Valid alternatives included adjusting the dose, trying a different antidepressant, adding lithium or revisiting psychological therapies.

However doctors were left in “an awkward position” by the lack of trials directly comparing these. Professor Mitchell declared no potential conflicts of interest.

As first appeared in Psychiatry Update, 13 March 2013


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