Joel A. Pava

Anxiety disorders in major depression

The prevalence and clinical impact of anxiety disorder comorbidity in major depression were studied in 255 depressed adult outpatients consecutively enrolled in our Depression Research Program. Comorbid anxiety disorder diagnoses were present in 50.6% of these patients and included social phobia (27.0%), simple phobia (16.9%), panic disorder (14.5%), generalized anxiety disorder ([GAD] 10.6%), obsessive-compulsive disorder ([OCD] 6.3%), and agoraphobia (5.5%). While both social phobia and generalized anxiety preceded the first episode of major depression in 65% and 63% of cases, respectively, panic disorder (21.6%) and agoraphobia (14.3%) were much less likely to precede the first episode of major depression than to emerge subsequently. Although comorbid groups were not distinguished by depression, anxiety, hostility, or somatic symptom scores at the time of study presentation, patients with comorbid anxiety disorders tended to be younger during the index episode and to have an earlier onset of the major depressive disorder (MDD) than patients with major depression alone. Our results support the distinction between anxiety symptoms secondary to depression and anxiety disorders comorbid with major depression, and provide further evidence for different temporal relationships with major depression among the several comorbid anxiety disorders.

Major depressive subtypes and treatment response

The purpose of this study was to investigate the relationships between depressive subtypes and response to fluoxetine treatment in a large cohort of outpatients. We studied 294 outpatients with major depressive disorder who were then treated with fluoxetine 20 mg/day for 8 weeks. Treatment outcome was evaluated with the Hamilton Depression Rating Scale (HDRS)-17, the Clinical Global Impressions-Severity, and with the HDRS-8; the latter is proposed to be a relatively more specific measure of depression severity than the HDRS-17. We assessed the relationships between degree of treatment response and several depressive subtypes (melancholic, atypical, hostile, and anxious depression, double depression, and depression with comorbid personality disorders), after adjusting for baseline depression severity. We found that nonanxious depressives (patients without any comorbid anxiety disorder) improved slightly but significantly more during treatment than anxious depressives on all outcome measures. Melancholic depression was associated with slightly less improvement on the HDRS-17 only, whereas the other subtypes of depression were not associated with differences in treatment outcome.

Attention deficit hyperactivity disorder in childhood among adults with major depression

The prevalence of attention deficit hyperactivity disorder (ADHD) with childhood onset and its relationship to course and treatment outcome of major depressive disorder (MDD) in adults was studied in 116 patients (ages 18-65) consecutively enrolled for treatment of MDD. Sixteen percent of the patient were found to meet full or subthreshold criteria for the DSM-III-R diagnosis of childhood ADHD. Twelve percent endorsed persistence of ADHD symptoms into adulthood. Depressed adults meeting criteria for childhood ADHD did not differ significantly from other depressed adults on any measures related to the chronicity or severity of the mood disorder, Axis I comorbidity, or response to acute antidepressant treatment. Our results are clinically important as they suggest that clinicians need to be aware of the possibility that a substantial proportion of patients with MDD may suffer from comorbid ADHD and that treatments need to include the targeting of possible residual ADHD symptoms in addition to those of depression.

Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications.

BACKGROUND Increasing attention has been directed in recent years to the detection and treatment of psychiatric co-morbidity among depressed individuals. The overlap of social phobia (SP) and avoidant personality disorder (APD) has been well recognized and a relationship between these disorders and depression has been suggested. METHODS The pattern and clinical implications of co-morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM-III-R criteria, were studied among 243 out-patients presenting with depression. RESULTS Overall, 26.7% of adults in our sample with MDD met criteria for SP and 28.4% for APD. Almost two-thirds of depressed adults meeting criteria for social phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed adults who met criteria for both SP+APD exhibited a significantly higher proportion of atypical depression (54.8%) compared with those with neither SP nor APD (31.1%). Among depressed patients, the co-occurrence of SP with APD was also associated with an earlier age of onset of MDD, a greater number of comorbid Axis I diagnoses, and greater impairment of social adjustment and assertiveness. CONCLUSIONS Results confirm the overlap of SP and APD in a depressed population and the high prevalence of these disorders in MDD. They suggest that depressed individuals with both SP and APD but not SP alone are at particularly high risk for atypical depression and for social dysfunction in excess of that caused by a current major depression.

Personality Disorder Comorbidity with Major Depression and Response to Fluoxetine Treatment

The relationship between depression and comorbid personality disorders is still poorly understood. The aims of this study were to examine differences in depression severity between depressed outpatients with and without comorbid personality disorders, to determine the effect of a fixed dose of fluoxetine on personality disorders, and to assess the predictive value of personality disorder diagnoses at baseline with regard to response to fluoxetine. Eighty-three outpatients with major depressive disorder (MDD) were assessed with a self-rating scale, the Personality Diagnostic Questionnaire-Revised (PDQ-R), before and after 8 weeks of treatment with fluoxetine 20 mg/day. The presence of a cluster B diagnosis before treatment predicted positive outcome as measured by the change in score on the modified 17-item Hamilton Rating Scale for Depression (HAM-D-17*). Following treatment, we found significant reductions in the frequency of most individual personality disorder diagnoses and total PDQ-R score. While patients no longer meeting criteria for cluster B personality disorders after treatment had similar reductions in depressive symptoms compared to those maintaining the diagnoses, subjects no longer meeting criteria for cluster A and cluster C diagnoses after treatment exhibited significantly greater decreases in depression severity than those who maintained the diagnoses. Overall, these results suggest that fluoxetine may be beneficial in the treatment of certain personality disorder traits in patients with MDD.

Consumption of Alcohol, Nicotine, and Caffeine Among Depressed Outpatients: Relationship With Response to Treatment

The authors present findings from the first investigation of the use of alcohol, nicotine, and caffeine in nonsubstance-abusing outpatients with major depressive disorder. The patients (N = 94) were assessed for their intake of alcohol, nicotine, and caffeine, and then treated openly for 8 weeks with 20 mg/day of fluoxetine. The degree of alcohol consumption at baseline was a significant predictor of poorer response to the antidepressant. This relationship remained significant even after adjusting for severity of depression at baseline. Even moderate levels of alcohol consumption appear to negatively affect pharmacologic treatment in depressed outpatients.

Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder

Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up.

Patterns of axis I comorbidity in early-onset versus late-onset major depressive disorder

BACKGROUND This study of a large clinical sample of depressed patients examined whether childhood onset as compared with adult onset Major Depressive Disorder (MDD) would confer a greater risk for Axis I comorbidity and whether childhood onset MDD would also differ from adult onset MDD in the pattern of comorbid disorders. METHODS We examined lifetime co-occurrence of Axis I disorders among 381 adult outpatients with MDD by Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P). Subjects were divided into childhood onset (n = 47), adolescent onset (n = 101) and adult onset (n = 233) MDD groups. RESULTS We found that the two early-onset groups exhibited significantly increased rates of Axis I comorbidity. The childhood onset group accounted for a disproportionately high percentage of depressed adults with two or more comorbid Axis I disorders. Social and simple phobias and alcohol abuse/dependence were significantly more prevalent among individuals with childhood onset MDD than among individuals with adult onset MDD. Alcohol abuse/dependence, but not anxiety disorders, was significantly more prevalent among adolescent onset than adult onset MDD groups. Panic, generalized anxiety, obsessive-compulsive and somatoform disorders were equally distributed across MDD onset groups. Comorbid disorders were much more likely to have followed onset of MDD among individuals with childhood compared with adult onset, except for social phobia which more frequently preceded the depression. The relative ordering among the comorbid conditions with respect to whether they followed or preceded MDD did not vary notably across the three age of onset groups. CONCLUSIONS We conclude that early-onset MDD is associated with an increased density of Axis I comorbidity that seems to be limited to specific disorders.

Psychosocial functioning during the treatment of major depressive disorder with fluoxetine

Background: Major depressive disorder (MDD) is associated with significant disability, having a profound impact on psychosocial functioning. Therefore, studying the impact of treatment on psychosocial functioning in MDD could help further improve the standard of care. Methods: Two hundred twenty-two MDD outpatients were treated openly with 20 mg fluoxetine for 8 weeks. The self-report version of the Social Adjustment Scale was administered at baseline and during the final visit. We then tested for the relationships between (1) self-report version of the Social Adjustment Scale scores at baseline and clinical response, (2) nonresponse, response and remission status and overall psychosocial adjustment at end point, (3) the number/severity of residual depressive symptoms and overall psychosocial adjustment at end point in responders, and (4) the time to onset of response and overall psychosocial adjustment at end point. Results: An earlier onset of clinical response predicted better overall psychosocial functioning at end point (P = 0.0440). Responders (n = 128) demonstrated better overall psychosocial adjustment at end point than nonresponders (P = 0.0003), while remitters (n = 64) demonstrated better overall psychosocial adjustment at end point than nonremitted responders (P = 0.0031). In fact, a greater number/severity of residual symptoms predicted poorer overall psychosocial adjustment at end point in responders (P = 0.0011). Psychosocial functioning at baseline did not predict response. Conclusions: While MDD patients appear equally likely to respond to treatment with fluoxetine, regardless of their level of functioning immediately before treatment, the above results stress the importance of achieving early symptom improvement then followed by full remission of depressive symptoms with respect to restoring psychosocial functioning in MDD.

Gender differences in Axis I comorbidity among depressed outpatients

OBJECTIVE The aim of our study was to assess gender differences in Axis I comorbidity in patients with a primary diagnosis of Major Depressive Disorder (MDD), as well as gender differences in age of onset of MDD. METHODS The presence of MDD, including age of onset, and of comorbid Axis I disorders were assessed in 396 depressed outpatients. RESULTS Women were significantly more likely than men to meet criteria for comorbid bulimia nervosa and for simple phobia, while men were significantly more likely than women to meet criteria for lifetime history of alcohol abuse/dependence and other substance abuse/dependence. No other significant gender differences in those comorbid Axis I disorders examined were observed. In addition, the age of onset of the first episode of MDD was significantly lower in women than in men. CONCLUSIONS Our findings are consistent with those of previous studies showing a greater prevalence of alcohol and substance abuse and dependence in men and of eating disorders in women.