R. N. Forgione

Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Prevalence, chronicity, burden and borders of bipolar disorder

Bipolar disorder (BD) has traditionally been thought of as an episodic condition, characterized by periods of hypomania/mania and depression. However, evidence is accumulating to suggest that this condition is associated with significant chronicity. For a large proportion of patients with BD, residual, sub-syndromal symptoms persist between major syndromal episodes, and studies have shown that many patients with bipolar disorder are symptomatic for approximately 50% of the time over follow-up periods of greater than 10 years. Moreover, while the prevalence of BD has been estimated to be around 1-2%, there is growing evidence that this may be a substantial underestimation. There are a number of reasons for this potential underestimation, including difficulties in diagnosis. Adding to the burden of BD is the issue of comorbidity, with an increased prevalence of many chronic conditions in those with a primary diagnosis of BD. Conversely, for many patients with chronic conditions, both medical and psychiatric, BD frequently exists as a comorbid secondary diagnosis. This issue of comorbidity complicates estimates of use of pharmaceutical agents for BD, such as mood stabilizers, which are known to be used off-label in conditions such as borderline personality or substance use disorder. We speculate that such off-label prescribing may not be truly off-label but may be instead fully justified by an overlooked secondary diagnosis of BD. Finally, we discuss the association of bipolar disorder with a significant economic burden, to the individual and to society, both due to the direct costs of medical expenditure and indirect costs such as loss of productivity and increased mortality.

Aripiprazole and ropinirole treatment for cocaine dependence: evidence from a pilot study.

BACKGROUND Currently, there is no specific pharmacological therapy with established efficacy for the treatment of cocaine dependence. The aim of this study was to determine the safety, tolerability and the effects of aripiprazole and ropinirole in patients with cocaine dependence. METHODS This randomized clinical trial of 12-week duration was carried out on 28 consecutive patients with cocaine dependence presenting for treatment. The diagnostic assessment was performed using ICD-9-CM criteria and Mini International Neuropsychiatric Interview. The Clinical Global Impression Scale, a Visual Analogue Scale to assess craving and a self-report questionnaire on the use of cocaine were administered at baseline and then weekly throughout the study. Urinalyses were carried out three times per weeks to search for benzoylecgonine. RESULTS Of the 28 study participants, 14 completed the protocol. Treatment discontinuation was unrelated with side effects. One patient required a dosage reduction of ropinirole because of sleepiness and one patient assigned to aripiprazole who reported moderate akathysia had the dosage reduced to 5 mg/day. Routine blood works did not show significant changes from baseline and the overall proportion of positive urinalyses for benzoylecgnonine did not differ significantly between treatments. Using linear mixed-effect models a significant decrease in craving was found in the overall sample (p<0.001). The mean number of cocaine administrations exhibited a faster decrease with aripiprazole compared with ropinirole (p=0.009). CONCLUSIONS Our pilot study indicates that cocaine craving decreases with both aripiprazole and ropinirole treatment but aripiprazole is more efficacious in reducing cocaine use.

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

Introduction: Several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission. Areas covered: This paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice. Expert opinion: Aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic–maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.

COMPARATIVE OUTCOMES AMONG THE PROBLEM AREAS OF INTERPERSONAL PSYCHOTHERAPY FOR DEPRESSION

Background: Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patients current depression contributed to IPT success. Methods: Patients meeting DSM‐IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17‐item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM‐IV Personality Disorders. Results: Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates. Conclusion: With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians. Depression and Anxiety, 2010.

Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice

Introduction: Asenapine is a sublingually administered second-generation antipsychotic with proven efficacy for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Its relatively favorable weight and metabolic profile, as well as the lack of appreciable activity at muscarinic cholinergic receptors and the sublingual administration are of clinical interest. Areas covered: This paper comprises a review and commentary regarding the use of sublingual asenapine in the treatment of acute manic and mixed episodes of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration with other medications are provided. Expert opinion: Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. Also, the sublingual administration reduces the risk of overdose when more than the prescribed tablets are swallowed. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.

Risperidone long-acting injection as monotherapy and adjunctive therapy in the maintenance treatment of bipolar I disorder

Importance of the field: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern. Areas covered in this review: This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder. What the reader will gain: The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research. Take home message: The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.

Development, acceptability and efficacy of a standardized healthy lifestyle intervention in recurrent depression

BACKGROUND Research evidence on the effects of integrated multifaceted lifestyle interventions for depression is scanty. The aim of the present study is to report on the development, acceptability and efficacy of a standardized healthy lifestyle intervention, including exercise, eating habits, sleep hygiene and smoking cessation in preventing relapses. METHODS One hundred-sixty outpatients with recurrent unipolar depression or bipolar disorder were recruited after achieving full remission or recovery from the most recent depressive episode. Patients were randomized to 3-months of usual care or to an intervention aimed at promoting a healthy lifestyle (HLI), as an augmentation of pharmacological maintenance treatment. Usual care consisted of clinical management visits. At the end of the intervention, follow-up visits were scheduled at 3,6,9 and 12 months. RESULTS During the intervention phase, 1 relapse occurred in the HLI group and 4 in the control group. Over the 12 months of follow-up, relapses were 5 in the HLI group and 16 in control group. Using an intent-to-treat approach, the overall percentage of relapses was 6/81 (7.4%) in the HLI group vs. 20/79 (25.3%) in the control group.. In a Kaplan-Meier survival analysis the risk of relapse was significantly lower in patients receiving the HLI intervention (log-rank test, p=0.003) over the 60 weeks of observation. The majority of patients assigned to HLI adhered to the program, and were highly motivated throughout the intervention. LIMITATIONS The retention rate was low because patients were recruited during the maintenance phase and the 1-year follow-up was relatively short to detect a long-term effect of HLI. CONCLUSIONS The HLI program proved to be efficacious in preventing relapses. Given the absence of contraindications and its cost-effectiveness in routine practice, the use of HLI should be encouraged to promote the well-being of patients with recurrent depression.

Practical guidance for prescribing trazodone extended-release in major depression

Abstract Introduction: Treatment of major depressive disorder aims for symptom remission and recovery of function, and involves a multifaceted approach including drug therapy, evidence-based psychotherapy, and electroconvulsive therapy, according to disease severity. Antidepressant monotherapy is generally the first-line approach for moderate to severe major depressive disorder (with or without psychotherapy). In some severe cases, patients may require the addition of antipsychotic therapy, electroconvulsive therapy, or antidepressant combination therapy. Areas covered: This article examines the use of trazodone in major depressive disorder, with a focus on practical guidance regarding the use of trazodone extended-release (Contramid®). Expert opinion: The extended-release once-a-day formulation of trazodone may provide a combination of efficacy and improved tolerability over other antidepressants and over the conventional immediate-release formulation.

Panic agoraphobic spectrum in psychiatrically healthy subjects: Impact on quality of life

Several studies have evaluated the quality of life (QOL) in patients with Panic Disorder (PD). For instance, the Epidemiological Catchment Area Study (ECA) assessed the quality of life (QoL) using the subjective evaluation of health, psychosocial functioning and financial status as parameters (Regier et al., 1984). Among the general population, people with PD or panic attacks reported a low level of physical health in 35% of cases and a low degree of mental health in 38% of cases, similarly to people suffering from Major Depressive Disorder (29% and 39% respectively), but more frequently than the in individuals not affected by any disorder (24% and 12% respectively). Furthermore, 27% of patients with PD were in need of some form of social or financial support in contrast to 16% of people suffering from depression and 12% of unaffected people. The National Comorbidity Survey (NCS) (Magee et al., 1996) found serious interference in activities in 27% of agoraphobic patients. For instance, the agoraphobic subjects reported an average of 1.1 days of work lost in the previous month due to their psychopathology. Several Authors have studied the relationship between PD and a worse quality of life and/or a worse ability to function. In a review on the topic, Mendlowicz & Stein (2000) provided an integrated view of the issue of quality of life in patients with anxiety disorders and concluded that the existing studies almost uniformly show a marked impairment of quality-of-life and psychosocial functioning in individuals with anxiety disorders. However, as noted by the Authors above, “despite the growing number of studies undertaken during the past 15 years, the investigation of quality of life in individuals with anxiety disorders is still in its infancy.” Rucci et al. (1993) evaluated the prevalence of subthreshold psychiatric disorders in primary care and their association with the patients health perception, disability in daily activities and psychological distress Subjects with subthreshold disorders reported levels of psychological distress, disability in daily activities and perceived health comparable to those of patients with full-fledged ICD-10 disorders. Despite the scientific and clinical importance of the topic, relatively few studies have evaluated the prevalence and impact of subthreshold affective disorders in general (Schotte & Cooper, 1999) and panic symptoms in particular (for instance Bellini & Galverni, 2003) in non psychiatric populations. Moreover, the literature on the relationship between sub-threshold or residual PD and quality of life is scant. To this end, we decided to investigate the impact of panic-agoraphobic “spectrum” on the quality of life of subjects who did not meet the criteria for a full blown PD. We adopted the definition of “spectrum” developed by Cassano and colleagues (Cassano & Pini, 2000; Rucci & Maser, 2000), which refers to a dimensional view of psychopathology that includes a broad array of manifestations of the target disorder, including its most severe symptoms as well as a range of more subtle features related to the core condition, which may include temperamental traits, prodromal indicators, or residual symptoms. Although they are frequently associated with specific DSM-IV disorders, these conditions are also found in individuals who have never met full DSM-IV diagnostic criteria. Our hypothesis for this study was that the presence of subthreshold panic-agoraphobic symptomatologies in otherwise healthy individuals would significantly impair the quality of life despite the absence of a full-blown PD diagnosis.