E V Nunes’s research while affiliated with Columbia University and other places

The authors examine the use of anticonvulsants/mood stabilizers To treat patients with substance use disorders. Although there is high comorbidity of bipolar and substance use disorders, there has been little research oil the use of these medications to treat bipolar disorders in patients who also have a substance use disorders. However, symptoms of bipolar disorders, such as irritability and mood lability, may be difficult to distinguish from The effects of acute and chronic substance use; therefore, reliable diagnostic methods will need to be developed Further a new, hypothesized syndrome, Explosive Mood Disorder, is described that may be distinct from the bipolar spectrum. It is characterized by childhood onset of temper out bursts and irritable mood that persists into adolescence and adulthood, is connected to marijuana use, and responds to divalproex sodium, The authors review studies of prevalence, comorbidity, family history, longitudinal course, and placebo-controlled trials of anticonvulsant medications to evaluate the validity and treatment implications of this proposed entity.

To report an open trial of divalproex sodium in 10 adolescents with chronic temper outbursts and mood lability. Ten adolescents meeting screening criteria for chronic temper outbursts and mood lability were followed for 5 consecutive weeks on open divalproex sodium treatment. Temper outburst frequency and mood swings severity at pretreatment and posttreatment were compared by using paired t tests. Subjects continued to be followed to judge persistence of response. All subjects showed clear improvement at 5 weeks and maintained it during follow-up while taking medication. Rapid relapse and recovery occurred in 5 of 6 patients who discontinued and then resumed medication. Divalproex sodium may be helpful in teenagers who have explosive tempers and severe mood swings, and benefits may generalize to school and family life.

We attempt to identify the time when patients whose conditions are unimproved while receiving antidepressants are unlikely to respond and should have their treatment changed. A total of 593 patients were studied. The course of treatment for patients was examined to determine the weeks at which patients who received drug therapy had a better chance of being rated as responders at the study end (week 6) vs patients who received placebo. At the end of week 3, 19 (32%) of the 59 patients who received drug therapy and 6 (10%) of the 57 patients who received placebo and who never minimally improved were rated as responders at week 6. For those who showed no improvement by week 4, the effects of drug therapy and the placebo were equal. Patients who received drug therapy and whose conditions were unimproved but who had been minimally improved at some point had a superior prognosis with drug therapy vs placebo until week 4. Of those unimproved at week 4 but minimally improved at some point previously, 20 (39%) of the 51 patients who received drug therapy vs 3 (8%) of the 36 patients who received placebo were rated as responders at week 6. Of the 75 patients who minimally improved while receiving drug therapy at the end of week 5, 33 (44%) had a chance of being rated a responder at the end of week 6 vs 9 (26%) of the 35 patients receiving placebo. Patients tolerant of an adequate dose, whose conditions have never been at least minimally improved by the end of week 4, should have their treatment regimen altered. These patients represented a minority of drug-treated patients in the sample studied (ie, 39/392 [10%]). Patients whose conditions minimally improve at some prior week but not after week 5 should have their treatment changed. Patients whose conditions minimally improve in week 5 should continue treatment until week 6.

Depressive disorders are commonly comorbid with alcoholism, particularly in treatment-seeking samples. If antidepressant treatment were safe and improved the treatment outcome in the subset of actively drinking alcoholics with depression, this would be of clinical importance. We conducted a randomized, 12-week placebo-controlled trial of imipramine hydrochloride combined with weekly relapse prevention psychotherapy. The subjects were 69 actively drinking alcoholic outpatients with current depressive disorders. The first onset of depression was either antecedent to the abuse of alcohol or occurred during prolonged periods of sobriety. Depression and drinking outcomes at 12 weeks, as well as their relationship, were measured. Imipramine treatment was safe and associated with improvement in depression in both adequately treated and intention-to-treat samples. While there was no overall effect on drinking outcome, patients whose mood improved showed decreased alcohol consumption that was more marked in those treated with imipramine. Imipramine treatment is effective for primary depression among actively drinking alcoholic outpatients, and may improve alcoholic outcome for those whose depression responds to treatment.

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.

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.

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.