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Biomedical subjects

J M Himmelhoch

Publications and source records attributed to J M Himmelhoch.

At least 19 recordsLinked to original sources
PubMed2001

Sertraline treatment of posttraumatic stress disorder: results of 24 weeks of open-label continuation treatment.

BACKGROUND: Posttraumatic stress disorder (PTSD) is typically associated with a high degree of chronicity, comorbidity, and psychosocial disability. The efficacy of sertraline in the acute treatment of PTSD has been confirmed based on the results of 2 large, placebo-controlled studies, but almost no prospective long-term treatment studies have been reported. METHOD: One hundred twenty-eight patients who completed 12 weeks of double-blind, placebo-controlled, acute-phase treatment for DSM-III-R-defined PTSD with sertraline were continued into a 24-week open-label continuation phase. Efficacy was evaluated using the endpoint change in the 17-item Clinician Administered PTSD Scale Part 2 (CAPS-2) severity score, the 15-item patient-rated Impact of Event Scale, and the Clinical Global Impressions-Improvement and -Severity of Illness scales as primary outcome measures. Treatment response was defined as > or =30% decrease in the CAPS-2 total severity score (compared with acute-phase baseline score) and a Clinical Global Impressions-Improvement score of 1 or 2. RESULTS: Ninety-two percent of acute-phase responders maintained their response during the full 6 months of continuation treatment. In addition, 54% of acute-phase nonresponders converted to responder status during continuation therapy. Over the 36-week course of acute and continuation therapy, 20% to 25% of the improvement in the CAPS-2 severity score occurred during the continuation phase. Sertraline was well tolerated, with 8.6% of patients discontinuing due to adverse events. A high pretreatment CAPS-2 score (> 75) predicted a longer time to response and a greater likelihood that response occurred after 12 weeks of acute treatment. CONCLUSION: The acute efficacy of sertraline is sustained in the vast majority of patients, and at least half of nonresponders to acute treatment will eventually respond to continued treatment.

Adult↗
PubMed1998

Social anxiety, hypomania and the bipolar spectrum: data, theory and clinical issues.

Reports in the literature indicate a subtle but consistent relationship between panic and bipolar II disorder. The possible connection between social phobia and bipolarity is less investigated. When we studied the treatment outcome of 32 social phobic patients administered either the reversible monoamine oxidase inhibitor (RIMA) meclobomide or the irreversible inhibitor MAOI phenelzine, we found that eighteen had remission > 50% of their socially anxious symptoms. Moreover, 14/18 of those improved became hypomanic, according to the Raskin Mania Scale (RMS) and the Young Mania Scale (YMS) coupled with expert clinical diagnosis. These findings possibly allude to a relationship of social phobia to bipolarity. Treatment with RIMA or MAOI exposed these subjects as having an atypical bipolar syndrome which is part of the bipolar spectrum. We then compared this special subset of subjects to the 18 socially phobic patients who failed to respond to RIMA's or MAOI's and to 26 patients with generalized anxiety disorder (GAD). Eleven of the 14 hypomanic responders gave histories of serious developmental deprivation (anaclisis); only 5/18 social phobics and 3/26 GADs without hypomanic responses had anaclitic histories. The author raises the possibility that anaclisis may have interacted with the impediment of volition of uncomplicated bipolar depression to produce social inhibition and anxiety. Finally, the author upholds the central role of depressive inhibition in bipolar disorder, which during antidepressant therapy often overshoots in a hypomanic direction; even in the absence of prior spontaneous hypomania, such disinhibition should classify this special subset of social phobic patients within the bipolar spectrum.

Adult↗
PubMed1992

Treatment of imipramine-resistant recurrent depression, IV: A double-blind crossover study of tranylcypromine for anergic bipolar depression.

OBJECTIVE: Few trials of monoamine oxidase inhibitors (MAOIs) in tricyclic-resistant depression have had double-blind conditions. In the authors' previous double-blind comparison of tranylcypromine and imipramine in anergic bipolar depression, tranylcypromine was significantly more effective. This investigation was a crossover study of nonresponders in the initial study. METHOD: The subjects were 16 outpatients with anergic bipolar depression. Fourteen had not responded to 4 weeks of treatment with at least 30 mg/day of tranylcypromine or 150 mg/day of imipramine, and two patients were crossed over because of intolerable side effects from the initial drug. The crossover medication was prescribed as in the initial double-blind study. RESULTS: Twelve patients were crossed over from imipramine to tranylcypromine; nine of them responded to tranylcypromine. Highly significant improvements were documented on the Hamilton, Beck, and Pittsburgh Reversed Vegetative Symptom Scales. Four patients were switched from tranylcypromine to imipramine, but only one responded. CONCLUSIONS: The high rates of response to tranylcypromine in both the initial and crossover double-blind studies document the efficacy of MAOI treatment for anergic bipolar depression. Moreover, the results further illustrate the utility of MAOIs in tricyclic-resistant depressions.

Adolescent↗
PubMed1991

Tranylcypromine versus imipramine in anergic bipolar depression.

OBJECTIVE: This investigation compared the efficacy of the monoamine oxidase inhibitor (MAOI) tranylcypromine with that of the tricyclic imipramine in the treatment of anergic bipolar depressive illness. METHOD: A controlled, double-blind comparison was used to study 56 outpatients who met operationalized criteria for anergic bipolar depression. Patients with bipolar I and II depression were equally distributed between comparison groups. Outcome was measured by the patient-rated Beck Depression Inventory and the clinician-rated Hamilton Rating Scale for Depression, Raskin Mania and Depression Scales, Clinical Global Impression Scale, and the Pittsburgh Reversed Vegetative Symptom Scale. Twenty-eight patients were treated with tranylcypromine and 28 with imipramine. Seventy-three percent of bipolar depressive patients screened for the study met criteria for anergic depression, consistent with previous findings from studies in bipolar illness that stretch back over 100 years. RESULTS: Tranylcypromine produced statistically significant superior outcome in terms of lower attrition, greater symptomatic improvement, and higher global response without increased risk of treatment-emergent hypomania or mania. CONCLUSIONS: The authors propose that the apparently superior efficacy of tranylcypromine in bipolar depression is specifically linked to anergia and reversed neurovegetative symptoms. Bipolar I and bipolar II patients had comparable outcomes, but bipolar I patients had a significantly greater risk of treatment-emergent mood swings. Although the relatively poor showing of imipramine warrants close scrutiny, these findings provide further documentation of the utility of MAOIs in patients presenting with anergia, motor retardation, hyperphagia, and/or hypersomnia.

Adult↗
PubMed1991

Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test.

OBJECTIVE: This study characterized objectively the hypersomnia frequently seen in the depressed phase of bipolar affective disorder. On the basis of previous work in sleep and affective disorders, it has been hypothesized that the hypersomnia is related to greater REM sleep. This hypothesis was tested by using a multiple sleep latency test to compare bipolar affective disorder with narcolepsy, a well-defined primary sleep disorder associated with known REM sleep dysfunction. METHOD: Twenty-five bipolar depressed patients were selected on the basis of complaints of hypersomnia. They underwent 2 nights of polysomnography followed by a multiple sleep latency test. Data on their nocturnal sleep and daytime naps were compared with similar data on 23 nondepressed narcoleptic patients referred for sleep evaluation. RESULTS: Despite their complaints of hypersomnia, no abnormalities were noted for the bipolar group in the results from the multiple sleep latency test. Contrary to the working hypothesis, REM sleep was notably absent during daytime naps in the depressed patients, in marked contrast to the findings for the narcoleptic group. CONCLUSIONS: The complaint of sleepiness in the hypersomnic bipolar depressed patient appears to be related to the lack of interest, withdrawal, decreased energy, or psychomotor retardation inherent in the anergic depressed condition, rather than an increase in true sleep propensity or REM sleep propensity.

Adult↗
PubMed1990

Plasma tranylcypromine: relationship to pharmacokinetic variables and clinical antidepressant actions.

Because the clinical actions of psychotherapeutic agents can be influenced by their pharmacokinetics, we investigated plasma tranylcypromine in relation to treatment outcome in 26 patients with bipolar depression. After oral administration of a tranylcypromine dose, plasma drug levels were measured hourly from 5-8 hours (N = 16) or 0-8 hours (N = 10) postdose, and pharmacokinetic parameters were calculated. Depressive symptoms were rated using the Hamilton Rating Scale for Depression (HAM-D), and subjects were categorized as responders, partial responders, or nonresponders, based on end-pair ratings. Twelve subjects were responders, seven were partial responders, and seven were nonresponders (mean scores = 3.2, 13.1, and 24.9, respectively); pretreatment HAM-D scores did not differ among the three groups. Tranylcypromine elimination (t1/2) was unrelated to clinical outcome. However, plasma tranylcypromine measured 5 hours postdose (5hTCP) was correlated with the end-pair HAM-D scores (r = 0.48, p less than 0.015) and was significantly higher in nonresponders than in responders (ANOVA, F = 4.7, p less than 0.02; Newman-Keuls test, p less than 0.05). For subjects who were studied from 0-8 hours postdose, the time to peak absorption (Tpeak), the area under the plasma tranylcypromine-versus-time curve, and the volume of distribution (Vd) were determined. Two subjects having delayed (3-4 hours) Tpeak also manifested elevated mean 5hTCP (63.9 vs. 34.1 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Sleep EEG and DST findings in anergic bipolar depression.

The authors report sleep EEG and dexamethasone suppression test (DST) findings for a homogeneous sample of anergic bipolar depressed outpatients (bipolar I, N = 7; bipolar II, N = 19) characterized by motor retardation, volitional inhibition, hypersomnia, or weight gain and sleep EEG findings for 26 age- and sex-matched normal control subjects. Sleep architecture was abnormal in bipolar depression, particularly with respect to little stage 1 sleep. The biological profile of an anergic episode of bipolar depression did not include a shorter than normal mean REM latency, poor sleep continuity, or abnormally low amounts of stages 3 and 4 sleep, and only three (13%) of 23 patients manifested cortisol nonsuppression.

Adult↗
PubMed1988

What destroys our restraints against suicide?

There seems to exist an inherent barrier to the achievement of any extreme biological state, be it massive intravascular coagulation, intense euphoria, or the inalterable decision to kill oneself. Moreover, defenses against suicide may in themselves be pathological, producing other types of maladaption. Indeed, certain lethality indicators possess a threshold, below which they act as a barrier against suicide. Wrist-cutting, self-treatment with drugs and alcohol, and psychosis itself all can play a defensive role in the organism's struggle for survival.

Adult↗
PubMed1987

Stimulation of cell membrane sodium transport activity by lithium: possible relationship to therapeutic action.

Because lithium is extruded from cells by means of coupled exchange for external sodium (Na+-Li+ countertransport), we hypothesized that clinical treatment with this agent could lead to significant augmentation of net cellular sodium influx. We therefore directly measured sodium influx in vitro using erythrocytes (RBCs) from 27 depressed bipolar patients. When cells were loaded with sufficient lithium to maximally stimulate Na+-Li+ countertransport activity (5.1 mmoles/1 RBCs), there was a significant 44% increase in mean sodium influx. To approximate clinical conditions more closely, we also studied sodium influx in a subset of eight subjects after loading cells with 0, 0.40, 0.66, and 1.55 mmoles lithium/1 RBCs. Over this range of lithium concentrations, sodium influx increased progressively. In separate experiments, we found that RBC sodium content measured in eight subjects did not change significantly during a 4-week course of lithium treatment. Thus, excess cellular sodium during such treatment may be extruded by increased activity of the membrane Na+-K+ pump, which has electrogenic properties and thereby could augment the membrane potential. In the nervous system, such an effect could stabilize cell membranes electrophysiologically, and possibly affect processes, such as behavioral sensitization or kindling, proposed to have a role in the development of recurrent affective disorders.

Bipolar Disorder↗
PubMed1987

Lest treatment abet suicide.

Epidemiologic data have identified risk factors, such as major depressive illness and sedative/alcohol addiction, that can help the clinician detect potentially suicidal persons. Evidence of subtle differences in the pattern of suicidality in bipolar and unipolar depressive illnesses has emerged. Suicide occurs early in unipolar episodes and intensifies along with increasing agitation and worsening melancholic symptoms. In bipolar depressive episodes, suicidality becomes an issue late in the course of a single episode, and illness severity and lethality are progressively aggravated by each affective relapse. Safe, effective treatment for suicide patients is the responsibility of the individual clinician and depends on neuropsychiatric variables, proper therapy, and direct and honest communication between patient and clinician. Adamant avoidance of division of primary clinical responsibility among cooperating specialists and clinician obstinancy when dealing with third parties can help prevent suicides. Early identification of psychosis, sedativism and subtle organicity are imperative. Pharmacotherapy usually equates to the fastest acting, most effective antidepressant drug, but some patients require electroconvulsive therapy to reduce suicidality. Involvement is the essence of psychotherapy in suicide management.

Adult↗
PubMed1986

Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects.

We investigated the pharmacokinetics of tranylcypromine, as well as the relationship between plasma levels of this agent and its effects on blood pressure and pulse rate. Tranylcypromine was absorbed rapidly after oral dosing, with the peak level being attained within 0.67 to 3.50 hours. Absorption was biphasic in seven of nine subjects. Elimination of tranylcypromine also was rapid, with a t 1/2 between 1.54 and 3.15 hours. From 2 to 7 hours after dosing, standing systolic and diastolic blood pressures were lowered and standing pulse was raised, compared with baseline. Onset of the effect on standing systolic blood pressure was correlated with the time of peak plasma tranylcypromine concentration. Maximum orthostatic drop of blood pressure and rise of pulse rate occurred 2 hours after dosing. Mean plasma tranylcypromine concentrations were correlated with mean orthostatic drop of systolic blood pressure and rise of pulse rate. Patients who have clinically significant hypotensive reactions to this agent may benefit from changes in their dose regimen aimed at minimizing peak tranylcypromine levels.

Administration, Oral↗
PubMed1985

A pharmacokinetic approach to the study of cell membrane lithium transport in vivo.

Although many previous investigations have focused on in vitro studies of lithium transport by erythrocytes (RBCs) of psychiatric patients, the extent to which such studies actually reflect the transport of this drug by other types of cells in vivo is unknown. To study lithium transport in vivo, pharmacokinetic analysis of plasma lithium concentration data was performed in four subjects who were given single oral doses of lithium carbonate (600 mg). The data were analyzed according to a two-compartment model, consisting of a central compartment (extracellular, including plasma) and a peripheral (intracellular) compartment. Rate constants for the transfer of lithium into (ki) and out of (ko) the intracellular compartment were calculated. In RBCs from the same subjects, lithium transport in vitro was also directly measured. Rate constants were determined for phloretin-sensitive transport (ks), which corresponds to Na+-Li+ countertransport activity, and residual passive "leak" diffusion (kr). In RBCs, these two pathways account for major components of lithium efflux and influx, respectively. To compare the in vivo and in vitro rate constant data, the ratios ko/ki and ks/kr were also calculated. There was a significant correlation between these two rate-constant ratios (r = 0.96, p less than 0.05), although the values observed in vitro were higher than those found in vivo. Because the in vivo rate constants reflect lithium transport by many types of cells in the peripheral compartment, this finding supports the idea that the RBC may provide a useful model for studying lithium transport processes that are also operative in other types of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Membrane Permeability↗
PubMed1985

Patterns of attrition for psychosocial and pharmacologic treatments of depression.

Patient characteristics associated with early termination from psychosocial and pharmacologic treatments of depression were delineated. Patients were 125 female primary nonbipolar depressives randomly assigned to 12 weeks of protocol treatment in one of four conditions: social skills training plus placebo; short-term psychotherapy plus placebo; amitriptyline alone; and social skills training plus amitriptyline. Results indicated that premature terminators from pharmacotherapy tended to be mildly depressed and intolerant of medication side effects. In contrast, dropouts from psychosocial treatment were more severely depressed and dissatisfied with the lack of early response which often accompanies interventions of this type. These findings may support the use of short-term psychosocial approaches in lieu of pharmacotherapy in mild nonendogenous depressions. However, antidepressant medication, either alone or in conjunction with psychosocial treatment, should continue to be considered the treatment of choice in more severely depressed melancholic patients.

Amitriptyline↗