William E. Falk

The antidepressant potential of oral S‐adenosyl‐l‐methionine*

S‐adenosyl‐l‐methionine (SAMe), a naturally occurring brain metabolite, has previously been found to be effective and tolerated well in parenteral form as a treatment of major depression. To explore the antidepressant potential of oral SAMe, we conducted an open trial in 20 outpatients with major depression, including those with (n= 9) and without (n= 11) prior history of antidepressant nonresponse. The group as a whole significantly improved with oral SAMe: 7 of 11 non‐treatment‐resistant and 2 of 9 treatment‐resistant patients experienced full antidepressant response. Side effects were mild and transient.

Tyrosine for depression: a double-blind trial

We treated 65 outpatients with RDC major depression in a randomized, prospective, double-blind comparison of oral L-tyrosine, 100 mg/kg/day, imipramine, 2.5 mg/kg/day, or placebo for 4 weeks. Tyrosine increased and imipramine decreased 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion significantly, but there was no evidence that tyrosine had antidepressant activity. The only side effect to achieve statistical significance was greater dry mouth with imipramine. MHPG excretion and plasma amino acid concentrations failed to predict or correlate with clinical improvement.

Fluoxetine versus trazodone in depressed geriatric patients.

A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients, but only 13 completed 6 weeks on study medication. Both agents were effective according to weekly and endpoint analyses, and there was no evidence of significant effects on blood pressure, pulse, or weight. Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression. (J Geriatr Psychiatry Neurol 1989;2:208-214.)

Effects of lithium on the kidney

ABSTRACT— We tested kidney function in 268 patients given lithium treatment for an average period of 37.6 months and in 59 manic‐depressive patients never given lithium. No patients suffered serious renal damage during the course of our observations. Maximum concentration capacity was lower and serum creatinine concentration higher in the lithium treated patients than in the controls, but the differences did not achieve statistical significance. Females had poorer concentrating ability than males, both among the control subjects and during lithium treatment. Concomitant antipsychotic drug therapy may affect concentrating ability and possibly glomerular function adversely.

Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant

S-adenosyl-L-methionine (SAMe), a putative antidepressant, is a naturally occurring substance whose mechanism of action is still a matter of speculation. It has been recently postulated that SAMe may increase the dopaminergic tone in depressed patients. Since dopamine inhibits both thyrotropin (TSH) and prolactin secretion, we investigated the effects of treatment with SAMe on the TSH and prolactin response to thyrotropin-releasing-hormone (TRH) stimulation in 7 depressed outpatient women (mean age: 46.1 +/- 7.2 years) and 10 depressed outpatient men (mean age: 38.0 +/- 10.0 years) participating in a six-week open study of oral SAMe in the treatment of major depression. At the end of the study, there was a significant reduction after treatment with SAMe in the response of both prolactin and TSH to TRH stimulation in the group of depressed men compared to pre-treatment values. On the other hand, in the group of depressed women, the posttreatment prolactin response to TRH did not appear to change when compared to pre-treatment and the TSH response to TRH challenge tended even to augment slightly after treatment with SAMe. Our results, at least in depressed men, seem to support the hypothesis of a stimulating effect of SAMe on the dopaminergic system.

CDP-Choline for the treatment of tardive dyskinesia: A small negative series☆

Based on the cholinergic-deficiency hypothesis of tardive dyskinesia (TD), we administered cytidine diphosphoryl choline (CDP-Choline) (a naturally occurring biochemical intermediary in the synthesis of phosphatidylcholine), 500 mg twice a day orally, to four women and one man with TD for 2 to 8 weeks in a double-blind, placebo-controlled crossover trial. Although the small sample size provides only limited power to detect a treatment effect, there was no evidence of efficacy, adverse effects, or changes in psychopathology.

An Open Trial of Maprotiline for the Treatment of Cocaine Abuse: A Pilot Study

Eleven consecutive severe cocaine abusers were treated openly with maprotiline. Nine completed a 7-week trial, and eight maintained abstinence for at least 1 month as outpatients. Treatment compliance and response appeared better than for a similar group of subjects treated without antidepressants.

Psychiatrists and their prescribing practices

Abstract Of all the variables that influence the decision to treat psychiatric symptoms with medication, the characteristics of the physician have been studied the least. A survey questionnaire was sent to one-third of the Massachusetts Psychiatric Society membership; 48% responded. They were asked to note their prescribing practice for four common psychiatric symptoms (anxiety, depression, mood swing, and though disorder) at three levels of magnitude (mild, moderate, and severe). The results were evaluated with the respondents age, sex, type of practice and treatment orientation acting as independent variables. At the mild and severe symptom extremes, there was generally little disagreement about the use of medication. In the moderate range, however, differences in ideology influenced practice significantly. Age and gender differences were also found to exert a significant influence.

Amoxapine for the Treatment of Psychotically Depressed Subjects: A Pilot Study

The treatment of psychotic depression remains controversial, although most studies suggest that the combination of an antipsychotic and an antidepressant agent is most beneficial. The authors describe an open-label study of the treatment of psychotic depression using amoxapine, an agent with both antidepressant and antipsychotic properties. Of the, six patients treated, two improved dramatically within the first week of treatment, whereas for the remaining four treatment had to be discontinued due to lack of efficacy or side effects. Amoxapine appears to be effective in some cases of psychotic depression, but side effects and known risks of treatment diminish its usefulness.

MEDICATION DECISIONS AND THE RISK OF TARDIVE DYSKINESIA

A random sample of one-third or 338 of the psychiatrists from the Massachusetts Psychiatric Society were surveyed. 48% or 162 completed a questionnaire composed of 10 vignettes, all describing the initial contact with an adult male schizophrenic outpatient who had been receiving chlorpromazine treatment and who showed no signs of tardive dyskinesia. The vignettes depicted varying durations of treatment, symptoms and courses of illness during prior treatment. Instructions focussed on the effect of the potential for developing tardive dyskinesia on decisions to continue to use chlorpromazine. We found that the primary consideration in medication decisions was to control active psychotic symptoms; a secondary one was to minimize the risk of tardive dyskinesia. When the psychosis was in remission, avoiding tardive dyskinesia was given higher priority than seeking to maintain the remission.