Faculty Bibliography

The clinical management of patients who present with anxiety syndromes combined with alcohol abuse or dependence is reviewed. A critical step is to make the differential diagnosis between alcohol-induced anxiety (principally alcohol withdrawal) and anxiety disorders per se. Interview and examination techniques useful in making this differential are presented. Clinical management of and pharmacotherapy for alcohol withdrawal are outlined. Anxiety disorders that can be comorbid with alcoholism include panic disorder, social phobia, obsessive compulsive disorder, generalized anxiety disorder, and posttraumatic stress disorder. Psychotherapeutic and pharmacotherapeutic measures for each of these in the setting of alcoholism are suggested, and various possible interrelationships between anxiety disorders and alcoholism are considered. Although anxiety disorders may contribute to the underlying etiology of alcoholism in some cases, alcohol abuse tends to take on a life of its own. Treatment of an anxiety disorder can rarely, if ever, be expected to cure alcoholism. Therefore, the need to institute simultaneous treatment aimed at establishing and maintaining sobriety is emphasized. Research on anxiety disorders and alcoholism is as yet inadequate to fully answer many clinical questions about their relationship and their appropriate diagnosis and management. More research is needed in this area.

We review the controlled trials of antidepressant treatment in methadone patients. Several studies show antidepressant effects, but none demonstrate clear improvement in drug abuse. This is contrary to "self-medication" but rather suggests depression is either independent or substance induced. Methodologic limitations are noted, especially reliance on cross-sectional mood assessment, which may select transient mood disturbances rather than true affective disorder. We review our previously published pilot study of imipramine in depressed methadone patients selected by lifetime history, and we report four year treatment course in the nine patients who responded favorably during that trial. Patients remained euthymic during imipramine treatment and relapsed to depression during attempts to taper it. This suggests imipramine had an enduring antidepressant effect. However, intermittent drug use remained a problem for several patients, suggesting depression and drug abuse are at least in part independent disorders. Placebo controlled replications, combinations of antidepressant medication with psychosocial interventions, and exploration of antidepressants as adjuncts in methadone detoxification, are suggested avenues for further research.

The objective of our study was to demonstrate that additional antidepressant benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not increased. Response between weeks 4 and 6 was studied among depressed outpatients randomly assigned to imipramine, phenelzine, or placebo under double-blind conditions. Patients were selected for analysis only if they did not have a dose increase after the start of the fourth week of treatment (day 22). Eighty-eight patients met this condition. Conditional probability analysis was performed. Nonresponders to 4 weeks (28 days) of treatment had a significantly greater likelihood of responding by week 6 if they were on phenelzine rather than placebo. The same is probably true for patients on imipramine. In research and clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of efficacy. Four weeks is probably also too short a trial of imipramine.

BACKGROUND:Data regarding effective treatment options for the minority of patients refractory to initial antidepressant trials are essential to guide therapeutic choices and to sustain the hope of patients and perseverance of clinicians. Few such data are available concerning the treatment of patients refractory to treatment with both a tricyclic antidepressant and a monoamine oxidase inhibitor given singly. METHOD/METHODS:In a study of mood reactive depressed patients, most of whom met Columbia criteria for atypical depression, 20 patients refractory to vigorous 6-week double-blind trials of both imipramine and phenelzine given singly were given clinician's choice open treatment. A chart review of course in open treatment was conducted. RESULTS:Eleven patients (55%) had a full response to subsequent treatments, principally continued phenelzine and the combination of phenelzine with amitriptyline. Another 6 (30%) had at least moderate benefit from a variety of other treatments. CONCLUSION/CONCLUSIONS:These data suggest that even among patients who have failed to respond to two vigorous trials of different antidepressants, at least half appear to benefit from other pharmacologic regimens.

Mood and anxiety disorders are common and treatable but may cause considerable morbidity if left untreated. This is especially so in opioid-dependent individuals, for whom diagnosis is difficult and rehabilitation easily compromised. Clinicians need guidelines to distinguish the patient with an independent mood or anxiety disorder from the more common anxious or depressed addict who is withdrawing, intoxicated or reacting to a life crisis. This article reviews the current knowledge of diagnosis, clinical presentation, and prevalence of mood and anxiety disorders common among opioid-dependent patients. It attempts to identify features of a patient's history that distinguish truly independent disorders and proceeds to a discussion of treatment approaches for this subgroup.

OBJECTIVE:This study assessed the impact of social ties on substance abuse treatment outcome. Two models which predict alternative hypotheses were evaluated. 1) Based on the self-medication model, it was hypothesized that social support would aid in coping with painful affect and decrease the need for drugs. 2) Based on a social learning model, it was hypothesized that drug use in the social network would threaten abstinence due to modeling and conditioning effects. METHOD/METHODS:Seventy methadone maintenance patients were given baseline measures of mood, stress, social support, and drug use in the network and followed prospectively for 3 months with weekly urine drug screens. RESULTS:Social support was correlated with positive affect (r = .59, p < .001), and stress with negative affect (r = .46, p < .001), but no measures of social support, affect, or stress correlated with the proportion of drug positive urines. However, patients with at least one drug user among the closest significant others had 63 +/- 38% positive urines versus 35 +/- 36% positive among those without a drug-using significant other (t = -3.2, p < .002). CONCLUSIONS:Substance use in the social network had a substantial negative impact on treatment outcome. Consistent with the social learning model and the traditional "persons, places, and things," this suggests interventions should get drug-using significant others into treatment and teach patients coping skills to reduce their negative influence.

Of 60 depressed alcoholics who completed an open trial of imipramine, 27 (45%) responded with improvement in both mood and drinking behavior, and eight (13%) responded after further dosage increases or treatment with disulfiram. In a subsequent 6-month, randomized discontinuation trial, four of 13 subjects (31%) relapsed during imipramine treatment and seven of 10 (70%) relapsed while taking placebo. This suggests a potential treatment approach for a high-risk subgroup of alcoholics.

We reanalyzed data from a larger, previously published study in order to directly address whether very chronically depressed patients could benefit from antidepressant medications. This study entered 598 depressed patients into a study randomizing patients to 6 weeks of double-blind treatment with imipramine, phenelzine, or placebo. Patients were assessed for chronicity on a four-point scale from "mostly well" to "virtually always depressed." The current analyses include only the 153 study completers who were rated as "virtually always depressed." In these patients, imipramine was effective for significantly more patients than was placebo (22 [46%] of 48 responding to imipramine vs. 9 [17%] of 52 responding to placebo; chi 2 = 9.50; p = 0.002), whereas phenelzine was significantly more effective than imipramine (37 [70%] of 53 responding to phenelzine; chi 2 = 5.96; p = .015). Patients with mild depression, early onset, or histories of panic attacks did not have substantially different outcomes than patients without these characteristics. These findings suggest that some chronically depressed patients may be good candidates for treatment with antidepressant medication. Because the majority (80%) of the sample met Columbia criteria for definite or probable atypical depression, too few chronic depressives were available to evaluate separately antidepressant efficacy in chronically depressed outpatients who did not have atypical depression. Hence, these results may be applicable only to patients with atypical depression.