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Biomedical subjects

D F Klein

Publications and source records attributed to D F Klein.

At least 145 records · Page 8Linked to original sources
PubMed1991

A survey of psychotropic medications not available in the United States.

The range of psychotropic medications available in the U.S. for the treatment of serious mental illnesses is limited. Many agents have been "me too" drugs, offering primarily side-effect differences, instead of new indications or mechanisms. As a result, patients refractory to the original drugs are not helped. Other patient populations (both mentally ill and addicted) have "fallen through the cracks" of the current U.S. psychotropic drug development process. The recent approval of chlorimipramine and clozapine demonstrates that real benefits for U.S. patients can be realized from judicious introduction of non-U.S. drugs. Many more psychotropic drugs developed and used in other countries are not available in the United States. Industrial and regulatory obstacles could be surmounted by the legislative innovation proposed. This survey identifies some specific non-U.S. drugs of interest.

Humans↗
PubMed1991

Improvement of phase III psychotropic drug trials by intensive phase II work.

Phase III drug trials are expensive, time-consuming procedures that too often are a disappointment, since the evidence for drug efficacy proves marginal and unconvincing. We believe that this can be remedied by attention to numerous correctable flaws during Phase II. These multiple problems require a structural solution. The development of expert, psychopharmacologic facilities that focus on deficient areas of Phase II studies so as to develop an adequate Phase III design should prove helpful.

Clinical Trials as Topic↗
PubMed1991

Obsessive compulsive disorder, depression, and fluoxetine.

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.

Adolescent↗
PubMed1990

Familial transmission of simple phobias and fears. A preliminary report.

Preliminary data from a blind direct interview family study indicate a significantly higher risk for simple phobia among first-degree relatives (n = 49) of simple phobic probands (who had no other anxiety disorder) as compared with first-degree relatives (n = 119) of never mentally ill controls (31% vs 11%, relative risk = 3.3). Female relatives were more likely to be affected than male relatives (48% vs 13%), though this difference did not reach conventional significance in an age-corrected analysis. Significant between-group differences were not found in risks for (1) other anxiety, affective, and substance abuse disorders, and (2) simple irrational fears that did not meet disorder criteria. The results suggest that simple phobia is a highly familial disorder that does not transmit increased risk for other phobic or anxiety disorders. The specificity of increased risk among the relatives of simple phobics is consistent with the distinction between simple phobia, social phobia, and agoraphobia. However, complete delineation of the transmissional relationship between these illnesses requires assessment of the extent to which risk for simple phobia can be transmitted by individuals with other phobic or anxiety disorders. Replication of these preliminary findings in larger clinically and epidemiologically selected samples is needed.

Adult↗
PubMed1990

Atypical depression, panic attacks, and response to imipramine and phenelzine. A replication.

In an initial study with 120 patients with reactive mood and associated atypical symptoms, phenelzine sulfate was superior to imipramine hydrochloride and placebo. Since their response to phenelzine appears to be unique, this suggests that atypical depression may be a distinct subgroup of unipolar depressive illness. Unexpectedly, the benefit of antidepressants was limited to patients who also had spontaneous panic attacks. To help establish the validity of this syndrome, a new sample of 90 atypical depressives was studied. The clinical and demographic characteristics of the original and replication sample were virtually identical at baseline. In addition, the treatment response with either placebo, imipramine, or phenelzine was also indistinguishable in the two patient groups. The outcome in the replication study supports the hypothesis that this may be a distinct unipolar depressive subgroup. In the replication sample, a history of panic attacks did not appear to be a relevant predictor. We discuss the explanations for this discrepancy in the two patient samples.

Anxiety Disorders↗
PubMed1990

Dopaminergic sensitivity and cocaine abuse: response to apomorphine.

Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed.

Adult↗
PubMed1990

Cardiac left ventricular hypertrophy and chamber dilatation in panic disorder patients: implications for idiopathic dilated cardiomyopathy.

Echocardiographic comparison of 35 panic disorder patients to 35 normal control subjects found subclinical increases of cardiac left ventricular chamber size in eight panic patients (and one control subject), and of left ventricular mass (corrected for body surface area) in seven panic patients. There was a significantly greater variance of left heart chamber size and corrected mass in panic patients compared with control subjects, without significant group mean differences. Consistent with a previously reported association of panic anxiety and idiopathic dilated cardiomyopathy, this study suggests that some healthy panic patients may have subclinical myocardial changes.

Adult↗
PubMed1990

Fluoxetine in panic disorder.

Twenty-five patients with a primary DSM-III-R diagnosis of panic disorder with or without agoraphobia were treated openly with the serotonin uptake inhibitor fluoxetine for up to 12 months. For most patients, treatment was initiated at 5 mg/day to minimize adverse effects previously reported with initiation at higher doses. Nineteen (76%) experienced moderate to marked improvement in panic attacks. Four (16%) were unable to tolerate fluoxetine due to adverse effects. Initiating treatment of panic disorder with low doses of fluoxetine may increase its acceptability and permit more patients to benefit from fluoxetine.

Adult↗
PubMed1990

Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression.

Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings.

Adult↗
PubMed1990

Fenfluramine augmentation of serotonin reuptake blockade antiobsessional treatment.

Seven patients who met DSM-III-R criteria for obsessive compulsive disorder and had only a partial response to the serotonin reuptake blockers fluoxetine, fluvoxamine, or clomipramine or were unable to tolerate therapeutic doses of these agents due to side effects underwent open treatment with fenfluramine augmentation. Fenfluramine is a serotonin releaser and reuptake blocker which is marketed as an anorectic agent. In doses of 20 to 60 mg/day, fenfluramine augmentation was well tolerated and resulted in a further decrease in obsessions and compulsions in six of these patients. Larger controlled studies are needed to confirm this finding.

Adult↗