Small Efficacy Differences Between Atypicals in Treating Schizophrenia
A recent meta-analysis examined all blinded clinical trials that directly compared second-generation antipsychotics, including 76 trials with 13,558 participants. The authors used the Positive and Negative Syndromes Scale (PANSS) as their primary outcome measure. On the PANSS, several differences emerged: olanzapine was significantly superior to aripiprazole, quetiapine, risperidone, and ziprasidone; risperidone outperformed quetiapine and ziprasidone. Fewer studies reported data separately on positive and negative symptoms. For positive symptoms, olanzapine and risperidone again outperformed quetiapine and ziprasidone. When considering only negative symptoms, quetiapine was superior to clozapine; no other significant differences emerged. In terms of dropout from trials due to inefficacy, olanzapine again outperformed risperidone, ziprasidone, and quetiapine while clozapine was superior to risperidone (Leucht S et al., Am J Psychiatry 2009; 166:152-163).
TCPR’s Take: Several statistically significant differences emerged between treatments, but they were small. For example, 16 patients would need to be treated with olanzapine rather than ziprasidone to avoid one dropout due to inefficacy. Other differences between treatments were of a similar magnitude; differences between olanzapine and risperidone were especially small. Only five studies included participants in their first episode of psychosis; no differences emerged in these studies. Treatment-resistant patients generally did not fare better on clozapine than comparator medications. However, clozapine patients on doses above 400 mg/day fared better than patients on risperidone. The authors stated they were surprised that clozapine did not consistently ourperform other antipsychotics, since other research has suggested that clozapine possesses superior efficacy relative to other atypicals for treatment-resistant patients, although this area of research remains controversial (McEvoy JP et al., Am J Psychiatry 2006;163:600-610).
Pharmaceutical sponsorship was not related to outcomes. Differences in side effects and cost appear more substantial than differences in efficacy, so clinicians should carefully consider these factors when treating patients with schizophrenia.
Unclear Relationship Between SSRI Use and Gestational Hypertension
A recent study investigated the relationship between the use of SSRIs prior to or during pregnancy and the development of gestational hypertension and preeclampsia. The study included a total of 5,731 women, of whom 199 took SSRIs two months prior to pregnancy and possibly during pregnancy. Nurses conducted telephone interviews with all participants within six months of delivery, collecting data on several relevant variables, such as smoking, alcohol consumption, dietary intake, diabetes, pre-pregnancy weight, and infertility treatment. Of women who took SSRIs during the study period, 19% developed gestational hypertension, compared to 9% of women who did not take SSRIs. The women at highest risk for gestational hypertension and preeclampsia were those who continued taking SSRIs after the end of the first trimester; women who continued SSRI treatment were 4.86 times as likely to report developing preeclampsia as women who did not take SSRIs during the study period (Toh S et al., Am J Psychiatry 2009;166:320-328).
TCPR’s Take: An accompanying editorial pointed to several limitations in the study (Yonkers KA, Am J Psychiatry 2009; 166:268-270). The researchers did not examine the medical records of participants; thus, it is impossible to know if participant’s recollections of preeclampsia or gestational hypertension were fully accurate. Child outcomes were not assessed in the study. Perhaps most important, the extent to which increased risk is due to SSRI exposure or due to underlying depression and/or anxiety is unknown. For more on the complicated relationship between antidepressants and pregnancy, see the February 2009 issue of TCPR.
Lamictal May Have Small Benefit for Bipolar Depression
Researchers (not paid by the drug company) examined data from GlaxoSmithKline’s database of clinical trials for lamotrigine (Lamictal) as a treatment for bipolar depression. Based on five placebo-controlled studies with a combined 1072 participants, Lamictal was found to outperform placebo by a statistically significant extent on some measures. Response rates on the Hamilton Depression Rating Scale (HAM-D) and Montgomery Asberg Depression Rating Scale (MADRS) favored Lamictal over placebo. Remission rates favored Lamictal on the MADRS but not the HAM-D.
Differences in response rates were small; using the Number Needed to Treat as a measurement of efficacy, we need to treat either 11 or 13 additional patients (depending on the method of assessment) in order to produce one treatment response more than placebo. Overall, Lamictal outperformed placebo in patients with severe depressive symptoms, but was not better than placebo for mild to moderate bipolar depression. This may have been due to the fact that there is less of a placebo response in severe depression (Geddes JR, 2009 Br J Psychiatry 2009;194:4-9).
TCPR’s Take: The data present a mixed picture. On some measures, the drug was effective. However, other measures found no advantage for Lamictal over placebo, and all benefits of the drug were quite modest. This meta-analysis confirms the prevailing wisdom that Lamictal is not a tremendously effective medication for acute bipolar depression, but may have a place in some severe episodes.