The superiority of antidepressant medication to cognitive behavior therapy in melancholic depressed patients: a 12-week single-blind randomized study.

OBJECTIVE: To pursue the previously long-standing but formally untested clinical view that melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone. METHOD: We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome. RESULTS: Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 61.1% vs. 34.4%, respectively [Number Needed to Treat (NNT) = 3.7] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 2.8) and remission (66.7% vs. 45.4%, NNT = 4.7) rates. CONCLUSION: As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study.

A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism.

OBJECTIVE: Olanzapine is a novel antipsychotic, which is effective against both the positive and negative symptoms of schizophrenia and causes fewer extrapyramidal adverse effects than conventional antipsychotics. The purpose of the present study was to assess the potential for a pharmacokinetic interaction between olanzapine and carbamazepine, since these agents are likely to be used concomitantly in the treatment of manic psychotic disorder. METHOD: The pharmacokinetics of two single therapeutic doses of olanzapine were determined in 11 healthy volunteers. The first dose of olanzapine (10 mg) was taken alone and the second dose (10 mg) after 2 weeks of treatment with carbamazepine (200 mg BID). Measurement of urinary 6beta-hydroxycortisol/cortisol excretion was used as an endogenous marker to confirm that induction of CYP3A4 by carbamazepine had occurred. RESULTS: The dose of olanzapine given after a 2-week pretreatment with carbamazepine was cleared more rapidly than olanzapine given alone. Olanzapine pharmacokinetic values for Cmax and AUC were significantly lower after the second dose, the elimination half-life was significantly shorter, and the clearance and volume of distribution were significantly increased. CONCLUSION: Carbamazepine has been shown to induce several P450 cytochromes including CYP3A4 and CYP1A2. Since CYP1A2 plays a role in the metabolic clearance of olanzapine, the interaction may be attributed to induction of CYP1A2 by carbamazepine, leading to increased first-pass and systemic metabolism of olanzapine. The interaction is not considered to be of clinical significance because olanzapine has a wide therapeutic index, and the changes in plasma concentration of olanzapine are within the fourfold variation that occurs without concern for safety in a patient population.

Six-month treatment outcomes in socially stable alcoholics: abstinence rates.

A randomly selected sample of 181 socially stable patients were followed for a period of six months after leaving alcoholism treatment. Collateral verification of drinking status was used to validate patient self-reports. A follow-up rate of 94% was achieved. For all patients, a continuous abstention rate (no drinking at all for the entire six-month period) of 61% was achieved, while 72% of the located patients were currently abstinent at the time of followup. For alcoholics with no other drug problems, a 66% continuous abstention rate was achieved, and 77% were currently abstinent at followup. These results suggest that alcoholism treatment can be effective for samples of socially stable alcoholics treated with multimodal treatments in a specialized, freestanding, alcoholism treatment facility.