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 patient's 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.

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. METHODS: Seventy-two IBS subjects were randomized to receive paroxetine CR (dose 12.5-50 mg/day) or placebo for 12 weeks. Subject selection was independent of abuse history. Sixty-one subjects completed the Sexual and Physical Abuse Questionnaire about their childhood abuse history. IBS symptoms were recorded using the Interactive Voice Response System (IVRS). Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS) and Clinical Global Impression (CGI) were also measured. The primary outcome was treatment response defined as > or =25% reduction in composite pain scores (CPS) on the IVRS from randomization to end of treatment. RESULTS: The rate of abuse history was 50.8% (n = 31/61). Baseline demographic clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were not associated with abuse history. After 12 weeks of treatment, subjects with abuse history showed significantly higher CPS (t = 2.422, P = 0.018) than subjects without a history and less mean change of CPS (t = 3.506, P = 0.001). In a logistic regression analysis, history of abuse did not predict treatment response as measured by > or =25% reduction in CPS (OR = 0.481, CI = 0.164-1.406, P = 0.181), while the drug status (paroxetine CR) was significantly associated with treatment response as defined by a CGI improvement score of 1-2 (OR = 12.121, CI = 2.923-50.271, P = 0.001). Abuse history did not predict CGI-I (Fisher's exact, P = 0.500) improvements during the trial. CONCLUSIONS: History of abuse did not appear to have any significant clinical correlates at baseline and did not predict treatment response. Further studies are needed to confirm whether SSRIs are effective in IBS patients irrespective of their abuse history.

Irritable bowel syndrome in psychiatric perspectives: a comprehensive review.

We comprehensively reviewed the irritable bowel syndrome (IBS) in terms of pathogenesis, psychiatric implications, general management and appropriate role of antidepressants, in particular selective serotonin uptake inhibitors (SSRIs) in the treatment of IBS. English language papers cited in MEDLINE and PychInfo from January 2000 to July 2006 were searched with a combination of the following key words: irritable bowel syndrome, 5-HT, pathogenesis, comorbid, psychiatry, treatment, psychotropic drugs, antidepressant, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and sertraline), tricyclic antidepressants, review, meta-analysis and placebo. The papers on IBS describing the clinical features, pathophysiology, evaluation, management, and clinical trials [randomised placebo-controlled trial (RCT), open-label study or case report] were selected for this review. Further literatures were also detected from references of the identified papers. The epidemiology, diagnostic criteria, pathophysiology, general management, bidirectional comorbidity, summary of currently available RCTs and open-label studies investigating antidepressant efficacy (focusing on SSRIs), and suggestions for SSRI use in IBS were relevantly synthesised based on through review of identified data. This article summarised an up-to-date clinical overview of IBS in psychiatric perspectives as well as to position a current role of SSRIs in the treatment of IBS. From this review, the routine use of SSRIs for IBS treatment cannot be conclusive due to a paucity of RCTs, although a handful of RCTs suggested a potentially beneficial effect of SSRIs over placebo.

Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study.

OBJECTIVE: The authors compared low-dose sustained-release bupropion with placebo for sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs). METHOD: Thirty adults who had received SSRIs for at least 6 weeks, who were euthymic, and who had sexual dysfunction as determined by a total score greater than 19 out of a possible 30 on the Arizona Sexual Experience Scale were randomly assigned to receive either 150 mg/day of sustained-release bupropion or placebo at 6:00 p.m. for 3 weeks. RESULTS: There were no significant differences between the sustained-release bupropion and placebo groups as measured by change in Arizona Sexual Experiences Scale or Hamilton Depression Rating Scale scores or side effects. CONCLUSIONS: Future studies should compare higher doses of bupropion for treating sexual dysfunction and should include a greater number of subjects.

Newly admitted psychiatric patient prescriptions and pharmaceutical sales visits.

There is much literature regarding the interaction of pharmaceutical sales representatives and physicians. However, there is little information available regarding their interactions with psychiatric residents. This paper attempts to quantify the impact of pharmaceutical sales visits upon prescriptions written for newly admitted patients in a psychiatric residency training clinic. A retrospective chart review of 47 consecutive patients was conducted. At the time of review all included patients had been admitted to the clinic for less than 3 months. Their psychiatric medication regimens were followed for 3 months. Initiation of new psychotropics was recorded. Data was also collected regarding the number of sales visits which typically occur at resident luncheons. Statistical analysis compared the number of new medication starts to the number of sales visits. Twelve pharmaceutical companies made sales visits. Eleven out of 12 companies' visits were statistically associated with an increase in new medication starts (p < 0.05). As the number of sales visits increased, a greater statistical significance was noted. This study is one of the first to quantify pharmaceutical industry's impact on psychiatric residents' prescribing practices. It appears that psychiatric residents preferentially start companies' medications shortly after sales visits. Furthermore, as sales visits increase in frequency, more of their medications may be started in newly admitted psychiatric outpatients.

Prescribing conventional antipsychotics at two Veterans Administration hospitals: are there geographical differences?

The medical records of 110 patients receiving conventional antipsychotics at two geographically distinct Veterans Administration hospitals (Syracuse, New York, and Omaha, Nebraska) were reviewed. The most common reasons for continuation of conventional antipsychotics were good response and patient or physician choice. Frequently, physicians did not discuss the reasons for continuing conventional antipsychotics or the availability of alternative therapies with their patients. Geographic differences in physicians' prescribing practices of conventional antipsychotics were apparent.

Cardiovascular side effects of novel antipsychotics.

Since the introduction of clozapine, several novel antipsychotic agents have been introduced and more are in Phase II/III studies. Because these agents are used clinically as first-line treatment, we need to be more familiar with their side-effect profiles. This manuscript reviews the cardiovascular side effects of currently available novel antipsychotics. The medications reviewed include clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. Guidelines are suggested for the use of these medications in clinical practice.

Side effects of antipsychotics in the elderly.

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Switching antipsychotic therapies.

BACKGROUND: Atypical antipsychotics are superior to conventional antipsychotics in improving positive and negative psychotic symptoms. Atypical antipsychotics do not exacerbate mood symptoms, and may improve mood symptoms and cognitive functioning; additionally, they have better adverse effect profiles than conventional antipsychotics. OBJECTIVE: To review the benefits of switching patients with schizophrenia or schizoaffective disorder from a conventional to an atypical antipsychotic, or from one atypical antipsychotic to another. In spite of the higher acquisition cost of atypical antipsychotics, overall treatment costs may decrease due to lower relapse and hospitalization rates. DATA SOURCES: A MEDLINE search (January 1977-January 1999) was conducted for articles written in English about efficacy, adverse effects, compliance, and pharmacoeconomics for atypical and conventional antipsychotics. STUDY SELECTION: Large, multicenter, double-blind, controlled studies were used for efficacy, safety, tolerability, and pharmaco-economic data. Where appropriate, recent review articles were also used. RESULTS: Atypical antipsychotics are superior to conventional antipsychotics in the treatment of schizophrenia. Atypical and conventional antipsychotics have different adverse effect profiles, costs, and compliance rates. CONCLUSIONS: Some patients may benefit by switching from a conventional to an atypical antipsychotic, from an atypical to a conventional antipsychotic, or from one atypical antipsychotic to another. Methods of switching antipsychotic therapies include tapering and cross-over strategies.

Weight gain associated with psychotropic drugs.

Weight gain is a common adverse effect of psychotropic drugs. Clinically significant weight gain puts the patient at risk for coronary heart disease, hypertension, Type II diabetes, dyslipidaemia and cancer, and can lead to non-compliance, with the probability of relapse and subsequent (re)hospitalization. This review focuses on specific drug classes such as antipsychotics, antidepressants, mood stabilizers and anxiolytics that have a propensity to induce clinically significant weight gain. Patients should be informed of potential drug-induced weight gain and instructed in the importance of weight management techniques (e.g., proper nutrition, physical exercise, behaviour modification). Individual patient-risk profiles should also be assessed. To ensure adherence to treatment, a proactive physician-patient relationship is essential. Patient compliance and quality-of-life issues are addressed. For appropriate medication selection, the clinician should consider the weight gain potential of various psychotropic agents.

Long-term adverse effects of novel antipsychotics.

The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.

Tardive dyskinesia: review of treatments past, present, and future.

The aim of this article is to review the theories purported to explain the pathophysiology of tardive dyskinesia (TD) and the various agents investigated for its treatment. The methods used included a review of studies in English, a Medline search, as well as a check of references listed at the end of the articles was conducted to obtain the relevant studies for review. The results show that vitamin E appears to be a promising agent both for the treatment and prophylaxis of TD. Complete remission has been reported with clozapine, but there is a need for further studies. There are cases reported of benefits with numerous miscellaneous agents, including electroconvulsive therapy, but there are no well-designed, substantiating studies. We conclude that there is no universally effective treatment for TD. Vitamin E is promising both for the treatment and possibly prophylaxis of TD. Clozapine therapy should be considered in patients refractory to traditional antipsychotics who develop TD. Judicious use of antipsychotics and periodic monitoring remain the cornerstone of therapy. None of the atypical antipsychotics (risperidone, olanzapine, clozapine, quetiapine) have been used long enough or adequately studied for their effects on TD.

Selective serotonin-reuptake inhibitors: an update.

Selective serotonin-reuptake inhibitors (SSRIs), including fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, represent an important advance in the pharmacotherapy of mood and other disorders. They are chemically unrelated to tricyclic, heterocyclic, and other first-generation antidepressants. SSRIs are the treatment of choice for many indications, including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder, because of their efficacy, good side-effect profile, tolerability, and safety in overdose, as well as patient compliance. A review of the literature was conducted using Medline and the terms "SSRIs," "fluoxetine," "sertraline," "paroxetine," "fluvoxamine," and "citalopram." Articles were limited to those published in English within the last 15 years. The search revealed that indications for antidepressants include unipolar depression, dysthymia, bipolar depression, treatment-resistant depression, depression in the medically ill, panic disorder, obsessive-compulsive disorder, eating disorders, social phobia, and premenstrual dysphoric disorder. One SSRI, fluoxetine, has demonstrated safety in pregnancy. Side effects of SSRIs include gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction.

Selective serotonin reuptake inhibitors in pregnancy and lactation.

Selective serotonin reuptake inhibitors (SSRIs) have become the agents of first choice in the treatment of depression because of their safe side effect profile. This paper reviews the current literature on the use of SSRIs in pregnancy and lactation concerning their safety. There are human studies that only used fluoxetine in pregnancy, which established its safety. SSRIs are excreted in breast milk, and their long-term effects on the newborn are unknown at this time. The decision to use SSRIs in pregnancy should be made on a case by case basis with active involvement of the patient in the informed consent process during which the risks and benefits are discussed and documented.