Biomedical subjects
Publications and source records attributed to F M Quitkin.
Of 17 consecutive patients receiving methadone maintenance treatment who had primary or chronic depression, nine (53%) improved in both mood and drug abuse after imipramine treatment. This finding suggests a potential for helping such dual-diagnosis patients reduce drug abuse and associated risk for HIV. Further controlled trials are warranted.
Of 60 cocaine misusers seeking outpatient treatment, 33 (55%) dropped out by 4 weeks. Dropouts were more likely to be male, Black or Hispanic, or with no history of primary depression. Completers were more likely to be White, female, or depressed. The implications of these findings and possible strategies for reducing the dropout rate are discussed.
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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.
Similar symptomatology has been described for both seasonal affective disorder (SAD) and atypical depression. For example, hyperphagia, hypersomnia, and intense lethargy are common to both, suggesting that they might be subtypes of the same disorder. If SAD and atypical depression are different manifestations of the same underlying pathophysiology, treatment effective for one might also benefit the other. Bright artificial lights (2500 lux, 6-8 a.m. and p.m.) were significantly less effective in treating eight patients diagnosed as having atypical depression without a seasonal pattern than 25 SAD patients. Differential treatment outcome suggests that SAD and atypical depression are separate disorders.
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.
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.
An open trial of lithium carbonate showed little efficacy for 10 cocaine abusers with bipolar spectrum disorders. It may be that the bipolar subgroup of cocaine abusers is heterogeneous and that only a fraction are lithium responsive.
The relationship of cerebral laterality to outcome of treatment with antidepressants was examined by comparing perceptual asymmetry in subgroups of depressed patients formed on the basis of clinical response to a tricyclic antidepressant (TCA) or a monoamine oxidase inhibitor (MAOI). Perceptual asymmetries of 63 unmedicated depressed patients were assessed for verbal and nonverbal tasks, using dichotic listening and visual half-field methods, and retests were obtained on 49 patients after about 6 weeks of treatment. There were significant differences between TCA responders and TCA nonresponders in dichotic listening and visual field asymmetries. Differences in perceptual asymmetry were specific to TCAs, in that no comparable differences existed between MAOI responders and MAOI nonresponders. Although perceptual accuracy improved following successful TCA treatment, abnormal perceptual asymmetries in TCA responders were present before and after treatment and may thereby represent state-independent characteristics.
A high-intensity fluorescent lighting system, tilted downward toward the head, and emitting negligible levels of ultraviolet radiation, was tested under two random crossover protocols in winter-depressed patients: 30-minute sessions at (a) 3,000 lux vs. 10,000 lux in early morning, and (b) morning vs. evening sessions at 10,000 lux. Judgment of clinical remission was based jointly on relative and absolute score improvements on a Structured Interview Guide for the Hamilton Depression Scale--Seasonal Affective Disorder Version (SIGH-SAD) and a set of supplementary atypical-vegetative items. Data are presented for 24 subjects who showed relapse upon withdrawal. An overall remission rate of 75 percent was found for morning light at 10,000 lux. The rates for evening light (25%) and 3,000 lux morning light (19%) were significantly lower. The remission rate for morning light treatment of 10,000 lux for 30 minutes approximately equalled 2,500 lux treatment for 2 hours (data from our earlier studies), suggesting a reciprocity between dosing dimensions of intensity and duration. No pathological changes were revealed by ophthalmological examinations given after 2 to 6 weeks of daily treatment.
Most previous studies of long-term maintenance therapy for bipolar illness simply compared proportions of patients experiencing recurrences. This method is inadequate because the length of time until a recurrence is not taken into account and because data from patients who withdraw prematurely from the study without a recurrence are either ignored or analyzed improperly. More appropriate survival analytic techniques were applied to the data from the National Institute of Mental Health Collaborative Study of bipolar patients treated with lithium carbonate, imipramine hydrochloride, or both. An interaction between treatment and the nature of the index episode (the episode that brought the patients into the study) was found. In patients with manic index episodes, both lithium and the combination were superior to imipramine. In patients with depressive index episodes, the combination was significantly superior to imipramine, whereas lithium was indistinguishable from imipramine. The latter finding differs from the original analysis, which found the combination to be no different from the other two treatments for patients with a depressive index episode.
Sixty patients who met Research Diagnostic Criteria for major, intermittent, or minor depressive disorder and had reactive mood without atypical symptoms were treated with imipramine hydrochloride, phenelzine sulfate, or a placebo. These patients, referred to as simple mood reactive depressives, were contrasted with previously published data from 180 atypical depressives. Atypical depressives had the presence of at least one vegetative atypical sign (hypersomnia, hyperphagia, leaden feeling, or rejection sensitivity) but were otherwise indistinguishable from simple mood reactive depressives. In contrast to the atypical depressives for whom phenelzine was effective and imipramine was relatively ineffective, both medications were equivalently good in simple mood reactive depressives. Since all groups did poorly when given a placebo and well when given phenelzine, the salient feature of atypical symptoms may be that they predict poor response to imipramine. Since the difference between imipramine and placebo depends on the diagnostic group, pharmacologic dissection suggests that atypical symptoms in patients with nonautonomous mood may delineate a qualitatively distinct subgroup.
One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.
The Structured Clinical Interview for DSM-III, Axis I was administered to a consecutive series of 30 cocaine abusers entering outpatient treatment. Another mental disorder was diagnosed only if its onset occurred before the onset of any substance dependence disorder. Diagnoses were made on a lifetime basis without regard to hierarchy. Most cocaine abusers had one or more additional diagnoses. We propose a model of two subtypes of cocaine abusers: (1) a primary affective disorder group, which may be split into bipolar versus unipolar or into severely versus mildly depressed subgroups; and (2) a group with other drug dependencies. The small n, limited sample, and methodological problems with diagnosis in the setting of substance abuse make these findings tentative. Future research should combine larger diagnostic studies with treatment trials to test whether such diagnostic subtypes have prognostic or treatment implications.
Bright artificial light has been found effective in reducing winter depressive symptoms of Seasonal Affective Disorder, although conclusions about the true magnitude of treatment effect and importance of time of day of light exposure have been limited by methodologic problems. Individual subjects' data from 14 research centers studying 332 patients over 5 years were analyzed with a pooled clustering technique. Overall, 2500-lux intensity light exposure for at least 2 hours daily for 1 week resulted in significantly more remissions--Hamilton Depression Rating Scale (HAM-D) score reduction of 50% or more to a level under 8--when administered in the early morning (53%) than in the evening (38%) or at midday (32%). All three times were significantly more effective than dim light controls (11%). Dual daily exposures (morning-plus-evening light) provided no benefit over morning light alone. In morning-evening crossovers, remission rates were 62% under morning light alone, compared with 28% under evening light alone, with a differential morning-evening response present in 59% of morning responders compared with 10% of evening responders (p less than 0.001). Remission rates with morning light were highest given low severity at baseline (HAM-D score of 10-16: 67% remission), as compared with moderate-to-severe cases (HAM-D score above 16: approximately 40% remission) where no morning-evening differences were found. Firmer conclusions await treatment studies with larger sample sizes and full assessment of atypical vegetative symptoms seen in winter depression but underrepresented in the Hamilton scale. Longer treatment course and greater light intensity may help clarify clinical response despite the impossibility of achieving a conventional blind placebo control.
Examined the influence of diagnostic subtype of depression on perceptual asymmetry for dichotic listening and visual tachistoscopic tasks. A total of 65 unmedicated patients with major depressive disorders and 30 normal controls were tested on a verbal and nonverbal task in each modality. Patients diagnosed according to the DSM-III with melancholia had abnormal perceptual asymmetry for dichotic nonsense syllable and complex tone tasks. In contrast, patients having a nonmelancholic "atypical depression" (reactivity of mood with preserved pleasure capacity and associated features) did not differ from normal controls on these tasks, but had an increased incidence of left handedness. Bipolar depression (history of hypomania) differed from unipolar depression in showing abnormal perceptual asymmetry for a tachistoscopic dot enumeration task. Alterations of perceptual asymmetry in melancholia and bipolar depression were consistent with hypothesized right hemisphere dysfunction.
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