Opiates were used to treat major depression until the mid-1950s. The advent of opioids with mixed agonist-antagonist or partial agonist activity, with reduced dependence and abuse liabilities, has made possible the reevaluation of opioids for this indication. This is of potential importance for the population of depressed patients who are unresponsive to or intolerant of conventional antidepressant agents. Ten subjects with treatment-refractory, unipolar, nonpsychotic, major depression were treated with the opioid partial agonist buprenorphine in an open-label study. Three subjects were unable to tolerate more than two doses because of side effects including malaise, nausea, and dysphoria. The remaining seven completed 4 to 6 weeks of treatment and as a group showed clinically striking improvement in both subjective and objective measures of depression. Much of this improvement was observed by the end of 1 week of treatment and persisted throughout the trial. Four subjects achieved complete remission of symptoms by the end of the trial (Hamilton Rating Scale for Depression scores < or = 6), two were moderately improved, and one deteriorated. These findings suggest a possible role for buprenorphine in treating refractory depression.

Ten menopausal chronically fatigued volunteers received 2 doses of pyrovalerone and a placebo in a double-blind, multiple crossover design. No significant drug-placebo differences were obtained, but the second administration of the drug at 20 mg TID was the most effective drug condition, producing significant improvement on the POMS factors of Fatigue, Confusion, and Tension-Anxiety, and significant weight reduction. The higher dose (40 mg TID) also reduced weight and Confusion, but produced many side effects. Optimal dose appears to be 60 mg daily. The absence of hypertensive effect may offer a special indication for use in obese-hypertensive patients who tolerate amphetamine poorly.

The data of this 10-year follow-up study provide evidence for the long-term stability of tardive dyskinesia and for the feasibility of maintenance neuroleptic therapy for chronic psychotic patients who have tardive dyskinesia.

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