Atypicals Roughly Equivalent to Molindone for Youth Psychosis
A recent NIMH-sponsored eight week trial compared two atypical antipsychotics, olanzapine (Zyprexa) and risperidone (Risperdal), to the first-generation antipsychotic, molindone (Moban) in the treatment of 116 youths with schizophrenia or schizoaffective disorder. There were no differences between the medications in terms of efficacy. Olanzapine was associated with significant increases in weight (average of 6.1 kg), total cholesterol, LDL cholesterol, insulin, aspartate aminotransferase, and alanine aminotransferase. Risperidone was also associated with increased weight (about 3.5 kg) and significantly increased prolactin levels. Molindone patients generally did not gain weight, but experienced akathisia at a higher rate than those taking atypicals, though they did not report more dystonic or parkinsonian symptoms (Sikich et al., Am J Psychiatry 2008;165:969-978).
TCPR’s Take: These results align with findings from several recent trials in adults that have also failed to demonstrate any significant efficacy advantage for atypicals over first-generation antipsychotics (FGAs). In the present study, all patients on molindone received prophylactic treatment with benztropine, which likely reduced the expression of parkinsonian side effects. Research has suggested that providing concomitant anticholinergic treatment is helpful in reducing such side effects and likely improving outcomes for adults taking FGAs (Rosenheck RA, Psychiatr Serv 2005;56:85-92). Side effect profiles differ significantly between FGAs and atypicals, but there appears to be little difference in efficacy overall between these drugs, particularly when lower-potency first-generation antipsychotics are used at moderate doses and concomitant anticholinergics are prescribed for patients taking FGAs.
Antidepressant Dose Escalation Not Found Helpful in Improving Outcomes
In the September 2007 issue of TCPR, we reviewed the very mixed literature on whether it makes sense to increase the dose of an antidepressant to achieve a response. We concluded that there is insufficient evidence, but that as long as you can avoid side effects, there is no compelling reason not to try dose escalation. A recent trial examined the effects of increasing the dosage of duloxetine (Cymbalta) for patients who did not achieve remission of depressive symptoms during acute treatment. After six weeks of treatment with Cymbalta 60 mg/day, non-remitted patients were randomly assigned to double blind treatment with either their original 60 mg dose plus placebo or an increase to 120 mg daily. At the end of eight weeks, there was no significant difference between the two groups in terms of efficacy, with 30% of participants in both groups achieving remission. Patients who exhibited a treatment response in the initial phase were more likely to show complete remission in the follow-up phase. The discontinuation rate due to adverse events was slightly, but not significantly, higher in the dose escalation group; however, sweating, chest pain, and tremor were significantly more common in patients whose dose was increased (Kornstein et al., J Clin Psychiatry 2008;69:1383-1392).
Psychotherapy and Medication Roughly Comparable in Treating Depression
Two recent meta-analyses examined the comparative efficacy of antidepressants versus psychotherapy in the treatment of depression and dysthymia (Cuijpers P et al., J Clin Psychiatry 2008, online ahead of print; Imel et al., J Affect Dis 2008;110:197- 206). In the acute treatment of depression, both reviews found that psychotherapy and medication did not differ in efficacy, although Cuijpers et al. found SSRIs superior to psychotherapy by a statistically significant but very small margin. In both reviews, medication was statistically significantly better than psychotherapy in treating dysthymia by a moderate effect size. Medication was linked to a significantly higher dropout rate than psychotherapy in the Cuijpers review. In studies that discontinued both treatments after a brief trial, psychotherapy led to longer term post-treatment gains than medication. Imel et al. also found that psychotherapy discontinued after an acute trial was as effective as medication continued in the longer-term, suggesting a prophylactic effect of short-term psychotherapy in reducing future episodes of depression.
TCPR’s Take: The general short-term equivalence of antidepressants and psychotherapy is in line with prior research, but some findings were surprising, particularly the notable superiority of medication in the treatment of dysthymia and the equivalence of short-term psychotherapy to longer-term medication treatment. The superiority for SSRIs over psychotherapy in the acute treatment of depression is interesting, but of questionable clinical significance given the very small difference in outcomes.