Motivation: Recently, one of my friends in psychiatry commented that the blog almost never touches upon psychiatry. And, that is unfortunately true despite the amount of psychiatric diseases in the medical wards. So, today, I wanted to examine the question of what happens when the SSRI just does not work after a good six weeks. Often, I have seen psychiatrists "augment" the treatment with a variety of anti-psychotics. Is there data behind the practice, and which anti-psychotic is the best one?
Paper: Nelson, J.C. and Papakostas, G.I. "Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials" Am. J. Psychiatry (2009) 166: 980-991.
Methods: Meta-analysis of double blind randomized trials comparing addition of atypical anti-psychotic versus placebo in patients with non-responsive major depression. Response was defined as >50% improvement in baseline scores of a depression rating scale (Montgomery-Asberg Depression Scale or Hamilton Depression Scale).
Results:
Trials: In total, 16 trials were analyzed with trial duration ranging from 4-12 weeks (9 trials lasted 8 weeks, 5 lasted 6 weeks, 1 lasted 12 weeks, and 1 lasted 4 weeks). The agents tested were olanzapine, risperidone, quetiapine, and aripiprazole. These anti-psychotics were added to anti-depressants which were typically a SSRI or SNRI.
Olanzapine: Overall, meta-analysis of 586 in treatment arm and 414 in control group. Odds ratio as listed below (higher OR with favorable treatment):
- Response: 1.39 (95% CI: 1.05-1.84), Remission: 1.83 (1.30-2.56)
- Adverse Effect: 3.85 (2.03-7.29)
Risperidone: Analyzed 211 in treatment arm and 175 in control group. Odds ratios as below:
- Response: 1.83 (1.18-2.82), Remission: 2.63 (1.51-4.57)
- Adverse Effect: 2.84 (0.91-8.91)
Quetiapine:Analyzed 677 in treatment arm and 352 in control group. Odds ratios as below:
- Response: 1.60 (1.24-2.08), Remission: 1.89 (1.41-2.54)
- Adverse Effect: 5.52 (2.71-11.24)
Aripiprazole: Analyzed 540 in treatment arm and 525 in control group. Odds ratios as below:
- Response: 2.07 (1.58-2.72), Remission: 2.09 (1.55-2.81)
- Adverse Effect: 2.68 (1.23-5.81)
Duration of Trial: No effect seen in response to drug based on duration ranging from 4 to 12 weeks.
Discussion: This meta-analysis both demonstrates the utility of anti-psychotics in treatment resistant depression and the equivalence for the four examined anti-psychotics (despite aripiprazole being the only FDA approved augmentation anti-psychotic). Interestingly, addition of anti-psychotics also resulted in increased adverse effects pretty uniformly. The meta-analysis did not describe the most common adverse effects (such as mild or severe or suicidal). Another limitation of this analysis is that only the acute phase of treatment (4-12 weeks) was examined. No data about maintenance phase was available although treatment is often extended to the maintenance phase as well. In summary, when faced with a depressed patient unresponsive to usual first line SSRI/SNRI agents, addition of an accessible anti-psychotic (whether risperidone or aripiprazole) is reasonable though patients should be monitored closely for severity of adverse effects.
Paper: Nelson, J.C. and Papakostas, G.I. "Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials" Am. J. Psychiatry (2009) 166: 980-991.
Methods: Meta-analysis of double blind randomized trials comparing addition of atypical anti-psychotic versus placebo in patients with non-responsive major depression. Response was defined as >50% improvement in baseline scores of a depression rating scale (Montgomery-Asberg Depression Scale or Hamilton Depression Scale).
Results:
Trials: In total, 16 trials were analyzed with trial duration ranging from 4-12 weeks (9 trials lasted 8 weeks, 5 lasted 6 weeks, 1 lasted 12 weeks, and 1 lasted 4 weeks). The agents tested were olanzapine, risperidone, quetiapine, and aripiprazole. These anti-psychotics were added to anti-depressants which were typically a SSRI or SNRI.
Olanzapine: Overall, meta-analysis of 586 in treatment arm and 414 in control group. Odds ratio as listed below (higher OR with favorable treatment):
- Response: 1.39 (95% CI: 1.05-1.84), Remission: 1.83 (1.30-2.56)
- Adverse Effect: 3.85 (2.03-7.29)
Risperidone: Analyzed 211 in treatment arm and 175 in control group. Odds ratios as below:
- Response: 1.83 (1.18-2.82), Remission: 2.63 (1.51-4.57)
- Adverse Effect: 2.84 (0.91-8.91)
Quetiapine:Analyzed 677 in treatment arm and 352 in control group. Odds ratios as below:
- Response: 1.60 (1.24-2.08), Remission: 1.89 (1.41-2.54)
- Adverse Effect: 5.52 (2.71-11.24)
Aripiprazole: Analyzed 540 in treatment arm and 525 in control group. Odds ratios as below:
- Response: 2.07 (1.58-2.72), Remission: 2.09 (1.55-2.81)
- Adverse Effect: 2.68 (1.23-5.81)
Duration of Trial: No effect seen in response to drug based on duration ranging from 4 to 12 weeks.
Discussion: This meta-analysis both demonstrates the utility of anti-psychotics in treatment resistant depression and the equivalence for the four examined anti-psychotics (despite aripiprazole being the only FDA approved augmentation anti-psychotic). Interestingly, addition of anti-psychotics also resulted in increased adverse effects pretty uniformly. The meta-analysis did not describe the most common adverse effects (such as mild or severe or suicidal). Another limitation of this analysis is that only the acute phase of treatment (4-12 weeks) was examined. No data about maintenance phase was available although treatment is often extended to the maintenance phase as well. In summary, when faced with a depressed patient unresponsive to usual first line SSRI/SNRI agents, addition of an accessible anti-psychotic (whether risperidone or aripiprazole) is reasonable though patients should be monitored closely for severity of adverse effects.
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