Praksh S. Masand

Aripiprazole in the Treatment of Depressive and Anxiety Disorders A Review of Current Evidence

Despite the availability of different classes of drugs for the treatment of depressive and anxiety disorders, there are a number of clinically significant unmet needs, such as a high prevalence of treatment resistance, partial response, subsyndromal symptomatology, recurrence and relapse. With the approval of atypical antipsychotics, which are associated with a lower adverse effect burden than typical antipsychotics, consideration of their off-label use for the treatment of affective disorders and various other psychiatric disorders has become a viable option. However, consideration should be given to the US FDA black box warning indicating that atypical antipsychotics may increase mortality risk, particularly in the elderly population with dementia-related psychosis.There has been much conjecture about the utility of these atypical drugs to facilitate traditional antidepressant therapy, either in combination (from the initiation of therapy) or as adjunctive therapy (in the case of partial/incomplete response). Nevertheless, at present, available evidence from randomized, placebo-controlled trials is sparse, and a formal risk/benefit assessment of the use of these agents in a nonpsychotic patient population is not yet possible.As a representative agent from the atypical antipsychotic class with a novel mechanism of action and a relatively low adverse effect burden, aripiprazole represents an interesting potential treatment for depressive and anxiety disorders. In this review, we focus on the rationale for the use of aripiprazole in these disorders.Preclinical data suggests that aripiprazole has a number of possible mechanisms of action that may be important in the treatment of depressive and anxiety disorders. Such mechanisms include aripiprazole action at serotonin (5-HT) receptors as a 5-HT1a partial receptor agonist, a 5-HT2C partial receptor agonist and a 5-HT2a receptor antagonist. Aripiprazole also acts as a dopamine D2 partial receptor agonist, and has a possible action at adrenergic receptors. Furthermore, aripiprazole may have possible neuroprotective effects.Clinical studies demonstrate that aripiprazole may be useful in the treatment of bipolar depression, major depressive disorder, treatment-resistant depression and possibly anxiety disorders. Clinical data also suggest that aripiprazole may have a lower adverse effect burden than the other atypical drugs.Future research may confirm the potential utility of aripiprazole in the treatment of depressive and anxiety disorders.

Childhood abuse and treatment response in patients with irritable bowel syndrome: a post‐hoc analysis of a 12‐week, randomized, double‐blind, placebo‐controlled trial of paroxetine controlled release

Objective:  Although irritable bowel syndrome (IBS) is frequently comorbid with childhood trauma, information on the clinical implications of this comorbidity is limited. We investigated whether a history of abuse was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in IBS.

Aripiprazole treatment for patients with schizophrenia: from acute treatment to maintenance treatment

The most current treatment guidelines for schizophrenia recommend more than 1 year of maintenance therapy after the first psychotic episode, and more than 5 years of maintenance therapy after multiple psychotic episodes. Approximately two-thirds of such patients are known to relapse within 1 year and almost 90% of such patients may recur within 2 years. To maintain adequate consistent treatment, balancing the efficacy and safety/tolerability should be one of the most important clinical issues. In this respect, aripiprazole appears to be a good treatment option owing to its comparable efficacy, favorable safety and tolerability profile, including low incidence of parkinsonian symptoms, lack of prolactin elevation, decreased adrenergic and anticholinergic side effects, less weight gain and low incidence of metabolic syndrome. Hence this article aims to summarize the currently available clinical trial data of aripiprazole published from a number of large-scale randomized controlled studies, including a newer formulation of intramuscular injection as well as a once-monthly intramuscular depot formulation, to update knowledge of treatment options in patients with schizophrenia.

Available therapies and current management of fibromyalgia: focusing on pharmacological agents.

Fibromyalgia (FM) is a chronic medical condition characterized by physical, psychiatric and psychological symptoms. Widespread pain, fatigue, sleep disturbances, heightened sensitivity, morning stiffness, decreased volition, depressed mood and a history of early abuse are frequently reported by patients with FM. Treatment of fibromyalgia is multidisciplinary, with an emphasis on active patient participation, medications, cognitive-behavioral therapy and physical modalities. No single medication has yet been found to sufficiently control all the symptoms of FM; currently available medication classes include antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, analgesics, hypnotic agents and anticonvulsants. Hence, treatment for patients with FM, including pharmacological and non-pharmacological approaches, should be individualized based on each patients clinical history, target symptoms and functional impairments. Although nonpharmacological modalities are also frequently used, recent research has focused on identifying more effective pharmacological treatments, particularly antidepressants and anticonvulsants. Furthermore, several new pharmacological agents have been now officially approved for the treatment of patients with FM. Thus, the purpose of this review is to help healthcare professionals make informed decisions about the appropriate use of a number of pharmacological treatments for patients with FM.

A 13-Week, Randomized Double-Blind, Placebo-Controlled, Cross-Over Trial of Ziprasidone in Bipolar Spectrum Disorder

Objective Features of bipolarity in a major depressive disorder sample were used to define a “bipolar spectrum disorder” population for treatment with a neuroleptic agent, ziprasidone. Methods Forty-nine acutely depressed patients were randomized to ziprasidone-washout-placebo or placebo-washout-ziprasidone in this double-blind, prospective, 13-week crossover trial. All patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for a major depressive episode and were positive for at least 3 predictors of bipolarity: family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early onset of depression (<age 20), failure to respond to antidepressants or antidepressant tolerance. The most common bipolarity inclusion criteria were antidepressant tolerance and nonresponse, and atypical depression. Approximately 52% received ziprasidone in monotherapy, 48% as adjunct to antidepressants. Results There was a small statistically nonsignificant benefit with ziprasidone compared with placebo on Montgomery Asberg Depression Rating Scale change [−1.5 (p = 0.48)]. Statistical carryover effects were observed. Conclusions Ziprasidone, alone or added to antidepressants, was not more effective than placebo in this population. A false-negative finding due to the crossover design is suggested by statistical carryover effects. Alternatively, this definition of bipolar spectrum illness may have been too nonspecific to show neuroleptic benefit, unlike other definitions, like “mixed depression.” Also, this study did not test potential neuroleptic efficacy without the potentially mood-destabilizing effects of antidepressants.