Can Omega 3s Prevent Psychotic Disorders?
Omega 3 fatty acids were once thought to be a possible treatment for mood disorders—but recent studies have been unimpressive. (See TCPR February 2010 for a review of omega 3 for depression.) In the latest test of the supplement’s psychiatric potential, researchers in Austria used it to prevent the onset of psychosis in high risk young adults.
Eighty-one patients between the ages of 13 and 25 at the outpatient psychosis detection unit of a large public hospital in Vienna were enrolled in this double-blind, placebo-controlled study. All participants in the study were considered at “ultra high risk” of psychotic disorder because they met at least one of three criteria: attenuated psychotic symptoms, transient psychosis, or “trait plus state” risk factors, defined as having a schizotypal personality disorder or a first degree relative with a psychotic disorder, and a decrease in functioning within the past year. Patients were randomized to 12 weeks of either 1.2 g/day of omega 3 or placebo. They were assessed for psychotic symptoms at four, eight, and 12 weeks, and then at six months and 12 months.
One year after the start of the study (and nine months after the treatment was discontinued) 11 of 40 patients (27.5%) who had taken placebo developed a psychotic disorder, as opposed to only two of 41 patients (4.9%) who were assigned to omega 3, a statistically significant difference. Most of those who converted to psychosis were diagnosed with either schizophrenia or schizophreniform disorder. The number needed to treat (NNT) with omega 3 to prevent one person from converting to psychosis was an impressively low four. The treatment was well tolerated, with no significant side effect differences between omega 3 and placebo (Amminger GP et al., Arch Gen Psychiatry 2010;67(2):146–154).
TCPR’s Take: If these results hold up in future studies, it would imply that omega 3 fatty acids are actually more effective than antipsychotic medication for prevention of psychosis. The sample size was fairly small (though large compared to many prior studies of psychosis prevention), and the included patients were carefully selected, both of which limit the generalizability of the results. But given that the treatment had no side effects, it seems reasonable to try it in pre-psychotic patients, or even as an adjunctive treatment in schizophrenia.
Antidepressants May Not Induce Mania in Bipolar Disorder
The frequency of antidepressant-induced mania has been elusive, with some studies finding high rates of manic switching and others finding very few or no manic episodes among patients taking antidepressants. A recent review sorted through this mixed bag of studies, examining the extent to which antidepressants induce mania or hypomania in both bipolar and unipolar depressed patients.
The authors performed a thorough literature search and included 30 randomized, placebo-controlled trials and 18 open trials in their analyses. The mean follow-up time was about five months. In patients with bipolar disorder, antidepressant use was associated with a slightly higher rate of mania or hypomania—15.3% on ADs vs. 13.8% not on ADs, but this difference was not statistically significant. Surprisingly, the use of mood stabilizers had no effect on the rate of antidepressant-related manic episodes. In patients with major depression, ADs led to a 6% switch rate, significantly greater than the 1.2% switch rate in patients not on ADs.
Risk of switching was higher for patients on tricyclics than SSRIs, though the difference was not statistically significant (Tondo L et al., Acta Psychiatr Scand online ahead of print).
TCPR’s Take: This study suggests that patients with bipolar disorder have a high risk of becoming manic or hypomanic over an average five month followup, but that the use of antidepressants does not increase the switch rate. The story is different in unipolar depression, in which antidepressants yield about a five-fold higher risk of manic/hypomanic switching. But before we conclude that antidepressants are perfectly safe in bipolar disorder, it is important to note that this is only one meta-analysis, and that other studies have reported that antidepressants can worsen the course of bipolar disorder. The authors of the meta-analysis themselves cautioned that the methodology of the included studies was flawed in many cases. Nonetheless, the findings should serve to increase our comfort level in prescribing antidepressants in bipolar depression.
D-Amphetamine or Caffeine May be Effective Augmentation of SSRIs for OCD
Previous research has shown that a single dose of d-amphetamine 30 mg (as monotherapy) relieves symptoms of OCD better than a placebo (Insel TR et al., Psychopharmacology 1983;80:231–235; Joffe RT et al., J Clin Psychopharmacol 1991;11:237–241).
In a new report, researchers sought to replicate these findings. They enrolled 24 patients with OCD who had residual symptoms even after at least 12 weeks on an SSRI or SNRI. All patients were randomly assigned to double blind treatment with either 30 mg/day of d-amphetamine or 300 mg/day of caffeine (in a pill that looked identical to the amphetamine, and was intended to be a placebo), in addition to their SSRIs/SNRIs, which they continued. While the trial lasted five weeks, only patients who showed some response after one week were allowed to continue in the full trial—meaning that only 13 of the original 24 patients completed the trial.
After five weeks, patients taking adjunctive amphetamine showed a mean improvement in the Y-BOCS score of 48%, while patients on adjunctive caffeine improved by 55% (the difference was not statistically significant). Researchers were surprised to find that d-amphetamine worked no better than caffeine for OCD symptoms. They wrote that caffeine’s good performance was probably not simply a placebo effect—instead, it may reflect damphetamine and caffeine’s shared neurotransmitter effect of releasing dopamine in the brain (Koran LM et al., J Clin Psychiatry 2009;70(11):1530–1535).
TCPR’s Take: This is a small study that did not include a true placebo arm, but these preliminary results are still intriguing. If both amphetamine and caffeine are actually effective for residual OCD symptoms (and we will need better studies to show this), then caffeine would probably be the preferable agent, given that it does not require a prescription and is unlikely to be abused. The 300 mg dose used in the study is the equivalent of almost two 8 oz cups of Starbucks coffee or 1.5 Vivarin caffeine pills (available over-the-counter at most drugstores for about $7 for 40).