Steven Lipper

Plasma prolactin changes following fenfluramine in depressed patients compared to controls: An evaluation of central serotonergic responsibility in depression

In an attempt to evaluate the responsiveness of the serotonergic neurotransmitter system in depression, fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls, and placebo was administered to 16 of the depressed patients in a double-blind paradigm. Plasma prolactin levels were measured prior to and for five hours following fenfluramine. Fenfluramine produced a significant increase in prolactin in both patients and controls. However, the prolactin response to fenfluramine whether measured as an absolute increase or percent increase from baseline was significantly less in depressed patients than controls. This difference remained equally statistically significant when age-and-sex-matched pairs of depressed patients and controls were compared. These results suggest that the central serotonergic system is less responsive in depressed patients than controls.

Preliminary study of carbamazepine in post-traumatic stress disorder

Ten patients meeting DSM-III criteria for post-traumatic stress disorder (PTSD) participated in a five-week open trial of carbamazepine. Seven patients manifested moderate to very much improvement, as shown on the Clinical Global Impression scale. Among the multiple symptoms associated with PTSD, nightmares, flashbacks, and intrusive recollections were selectively reduced in intensity and frequency. The results suggest that a kindling model or a model of a paroxysmal disorder may be applicable to PTSD.

Comparative behavioral effects of clorgyline and pargyline in man: A preliminary evaluation

The antidepressant and other behavioral effects of clorgyline, a preferential inhibitor of monoamine oxidase (MAO) type A, were compared with those of pargyline, a preferential inhibitor of MAO type B, in 16 depressed patients. In a subgroup of more severely depressed patients, clorgyline treatment for 4 weeks resulted in significant improvement on both observer-rated and self-rated scales, while minimal changes occurred during pargyline treatment. Similarly, in a crossover study that included 8 patients examined with multiple scales, clorgyline had generally greater antidepressant and antianxiety effects than did pargyline, although pargyline had some activating effects and also tended to produce more side effects. MAO type A inhibition may be more important than MAO type B inhibition for antidepressant efficacy.

Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man.

During 4 weeks of treatment with clorgyline, a selective MAO-A inhibitor, platelet monoamine oxidase (MAO) activity was unchanged. During a similar 4-week crossover treatment period with pargyline, a selective MAO-B inhibitor, platelet MAO activity was essentially completely inhibited in the same individuals. The differential effects of the two drugs on platelet MAO, which consists exclusively of the MAO-B form, suggests that the in vitro selectivity of clorgyline, and possibly of pargyline, on MAO-A and MAO-B may be maintained in vivo during long-term administration in man. Reductions in blood pressure, heart rate, and plasma amine oxidase activity were generally similar in magnitude during treatment with both drugs, however, suggesting that either these effects are nonspecific consequences of both MAO-A and MAO-B inhibition, or that pargyline also inhibited MAO-A activity.

ELEVATION OF PLASMA-PROLACTIN BY MONOAMINE-OXIDASE INHIBITORS

Plasma-prolactin levels doubled in depressive patients treated with the monoamine-oxidase inhibitors, clorgyline and pargyline. The absence of significant changes in plasma-cortisol in the same patients suggests that the increases in prolactin are not attributable to non-specific effects of stress.

Lifetime sexual and physical victimization among male veterans with combat-related post-traumatic stress disorder.

ABSTRACT Because of the high prevalence of post-traumatic stress disorder (PTSD) among veteran men and the limited research on victimization in this group, we recruited 133 male veterans with combat-related PTSD from a psychiatric inpatient unit and assessed them for lifetime physical and sexual trauma. Results indicated that 96% of the sample had experienced some form of victimization over their lifetimes; 60% reported childhood physical abuse, 41% childhood sexual abuse, 93% adulthood physical assault, and 20% adulthood sexual assault. In the preceding year alone, 46% experienced either physical or sexual assault. These findings support the need for routine inquiry into the histories of noncombat victimization in this cohort. Determining the lifetime history of trauma exposure may have implications for vulnerability to subsequent development of PTSD and the risk of future violence.Because of the high prevalence of post-traumatic stress disorder (PTSD) among veteran men and the limited research on victimization in this group, we recruited 133 male veterans with combat-related PTSD from a psychiatric inpatient unit and assessed them for lifetime physical and sexual trauma. Results indicated that 96% of the sample had experienced some form of victimization over their lifetimes; 60% reported childhood physical abuse, 41% childhood sexual abuse, 93% adulthood physical assault, and 20% adulthood sexual assault. In the preceding year alone, 46% experienced either physical or sexual assault. These findings support the need for routine inquiry into the histories of noncombat victimization in this cohort. Determining the lifetime history of trauma exposure may have implications for vulnerability to subsequent development of PTSD and the risk of future violence.

The central noradrenergic system and affective response to MAO inhibitors

1. In humans, norepinephrine (NE) has been postulated to be involved in the regulation of mood and behavior and to be altered in patients with manic-depressive illness. 2. Recent methodological advances have made possible a more direct assessment of central noradrenergic activity by the accurate measurement of the small amounts of NE and of the enzyme responsible for the conversion of dopamine to NE, dopamine-beta-hydroxylase (DBH), found in cerebrospinal fluid (CSF). 3. Cerebrospinal fluid samples were obtained from depressed patients both before and after treatment with two monoamine oxidase-inhibiting antidepressant drugs, clorgyline and pargyline. 4. Patients were rated twice daily by nursing staff on a modified 15-point scale for severity of global depression and anxiety. Patients were also rated using the Hamilton depression rating scale. 5. High negative correlations were observed between the drug-related changes in CSF NE and the changes in depression ratings on both the global ratings (r = -.95, p less than .001) and the Hamilton rating scale (r = -.81, p less than .01). Changes in NE were also highly correlated with changes in global anxiety ratings (r = -.85, p less than .01) calculated on the basis of changes from baseline for each measurement. Drug-related changes in CSF DBH similarly showed negative correlations with clinical response (r = -.79, r = -.38, r = -.68 respectively). In contrast, no significant correlations were found when drug-related changes in CSF MHPG were compared to changes in clinical state.

The response of depressed inpatients to isocarboxazid.

Fifty-six inpatients with unipolar depression completed treatment with isocarboxazid. In comparing the differences between responders and nonresponders, it was found that psychomotor retardation, pathological guilt, daily persistence of unremitting symptoms, phobic anxiety, dexamethasone suppression test nonsuppression, and neuroticism were significantly more common among nonresponders. Reactivity of mood, blaming others, and extraversion were more common in responders. Total endogenous depression scores on the Newcastle 1, Newcastle 2, and Michigan scales were also significantly higher in nonresponders. Attained platelet monoamine oxidase inhibition was similar in both groups.

PSYCHOACTIVE DRUG EFFECTS ON PLASMA NOREPINEPHRINE AND PLASMA DOPAMINE β-HYDROXYLASE IN MAN

Chronically-administered clorgyline, pargyline and fenfluramine produced marked reductions in plasma norepinephrine (NE) levels in depressed patients. In contrast, the acute administration of (+)-amphetamine and fenfluramine led to modest increases in plasma NE in depressed patients. Lithium carbonate treatment tended to be accompanied by higher plasma NE, but like plasma dopamine β-hydroxylase changes with all of these drugs, there were large variations in response in individual patients, and statistically-significant alterations were not observed during treatment.

Cardiovascular changes accompanying MAO inhibition in man

Drugs which inhibit monoamine oxidase (MAO) in vivo produce changes in the metabolism of over ten amines whic are substrates for this enzyme. Some physiologic and behavioral changes in animals and man occur as direct consequences of these amine metabolism alterations, while others occur later and appear related to adaptational responses in amine-containing neurotransmitter systems. Our group has been interested in whether the recently accumlating knowledge about substrate-selective subtypes of monoamine oxidase might have clinical implications. Much of the information regarding MAO substrate selectivity has been obtained in vitro or under conditions of acute MAO-inhibitor administration in rodents, and has indicated that serotonin, norepinephrine and dopamine are preferentially deaminated by MAO type A, while phenylethylamine, phenylethanolamine, tele-methylhistamine, benzylamine and o-tyramine are more avidly deaminated by MAO-B (for reviews see Fowler, et al., 1978; Murphy, 1979). We have been systematically studying the effects of longer-term administration of several selective MAO-inhibitor drugs in animals (Campbell, et al., 1979) and man (Murphy, et al., 1979).