Long-term Pharmacological Treatment Research Articles

Treatment research in bipolar disorder: issues and recommendations.

Bipolar (manic-depressive) disorder is one of the most common of the severe mental illnesses. Officially recognised forms comprise type I (with mania), type II (with hypomania), cyclothymia and a rapid-cycling subtype. International lifetime prevalence estimates are 1 to 5% of the general population, and bipolar disorder accounts disproportionately for idiopathic psychoses. Psychiatric and substance-abuse comorbidities are common complications, and mortality rates are increased as a result of high suicidal risks, accidents, complications of substance abuse and increased fatality of stress-sensitive medical illnesses. Complex and labile symptomatic presentations, a tendency for patients to deny illness and reject treatment, and diagnostic heterogeneity severely complicate the design, conduct and interpretation of experimental treatment trials in bipolar disorder. Progress in the short-term treatment of mania with certain antiepileptic drugs and atypical antipsychotic agents has advanced greatly in recent years; however, long-term treatment trials other than with lithium remain rare, as are studies of type II disorder, bipolar depression and mixed states, and there is limited information on treatment effectiveness against comorbidity, dysfunction and mortality. There is a growing realisation that bipolar disorder represents a major, largely unmet, international public health challenge and that innovative methods for carrying out reliable and generalisable long-term pharmacological treatment trials, alone and in combination with cost-effective psychosocial and rehabilitative interventions, are urgently required.

Epidemiology, clinical features, and immunology of the "intrinsic" (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis).

Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

Long-term pharmacological treatment of generalized anxiety disorder.

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders and has a poor prognosis, although it is often thought to be a minor complaint. This disorder has a chronic course of 5-15 years and longer. Long-term treatment with the commonly used benzodiazepines is controversial because of concerns over tolerance and dependence. We performed a thorough search of the literature for clinical trials of a duration of over 2 months conducted in patients with generalized anxiety disorder in order to identify any successful long-term treatment of this disorder. Only eight long-term reports of studies conducted in well-defined homogeneous groups of patients diagnosed with generalized anxiety disorder were found with the methodology of these studies presenting a number of limiting factors. The results are inconclusive and no reference drug could be identified. In addition, an adequate evaluation of the long-term treatment of GAD has not yet been performed.

PHB9 Use of Centralized Pharmacy Records in A Managed Care Organization to Determine Effect of Educational Material on Hormone Replacement Therapy Patient Compliance

Post-menopausal hormone replacement therapies (HRT) represent a significant long-term pharmacological treatment that is associated with multiple beneficial clinical outcomes. However, HRT is associated with a significant reduction in patient compliance over time. OBJECTIVE: To determine the impact of periodically mailed patient educational materials on HRT compliance. METHODS: Using centralized pharmacy records from a managed-care organization, both retrospective baseline (12 months preceding mailings) and prospective (12 months following mailings) compliance indices were analyzed for three cohorts of patients: Cohort A = patients who were receiving material prior to program initiation; Cohort B = patients who were offered material but declined; and Cohort C = patients who had not previously received material but elected to do so during the study period. Compliance indices included assessment of MEDINT (number of days of medication), MED-TOT (total medication) and MED-OUT (days without medication). Patients were identified as “compliant” if they had a MED-TOT>75% or a MED-OUT<25%. RESULTS: 584 patients (Cohort A = 149, Cohort B = 245, and Cohort C = 190) were included in analyses. During the retrospective baseline period, all three cohorts had statistically similar compliance indices. Analyses of data collected during the prospective period indicated that, compared to Cohort B, significant (p < 0.01) between-group improvements in each of the compliance indices were observed. Furthermore, the greatest overall improvements from baseline were observed in Cohort C, and Cohort C demonstrated a significant (p < 0.01) increase in number of “compliant” patients compared to Cohort B. CONCLUSION: These results suggest that educational material significantly improves patient compliance, and the effect can be directly observed by assessing centralized pharmacy records.

Long-Term Pharmacologic Treatment of Morbid Obesity in a Community Practice

To determine the safety, efficacy, and metabolic changes in patients with morbid obesity treated with d,l-fenfluramine and phentermine in an open-label trial. In patients with a body mass index (BMI) =40.0 kg/m 2 (N = 298) who sought assistance at a private medical practice for treatment of obesity, 60 mg of d,l-fenfluramine and 15 to 30 mg of phentermine resin were administered daily in an open-label trial, without placebo controls, for up to 24 months. The setting was a community-based private practice. Study subjects were given instructions for a 1,200 to 1,400 kcal/day diet, exercise, and behavior modification. Follow-up included a monthly medical visit, behavior modification group attendance, quarterly laboratory evaluation, and electrocardiographic monitoring. BMI decreased from 45.8 kg/m2 to 37.4 kg/m2 (P<0.0001) in those who completed 12 months of treatment and to 38.2 kg/m2 (P<0.0001) in those who continued the protocol for 24 months. Statistically significant decreases in fasting blood glucose, total and high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, and fasting insulin concentrations were noted. The dropout rate was 42.3% at 12 months and 69.8% at 24 months. The most common reason given for discontinuing participation in the study was "success" with the program (mean BMI loss of 7.8 kg/m2). Five patients discontinued treatment because of side effects. No laboratory or electrocardiographic abnormalities were noted that could be attributed to the medications. No statistically significant regain of weight occurred in those who completed 12 or 24 months of treatment. In this study, treatment of morbid obesity with d,l-fenfluramine and phentermine was safe and efficacious in promoting and maintaining weight loss. Moreover, statistically significant changes were noted in metabolic variables associated with risk of heart disease. Future efforts must focus on methods to improve long-term compliance.

Generalized Anxiety Disorder: Longitudinal Course and Pharmacologic

Generalized anxiety disorder (GAD) is a high-prevalence disorder with a relatively early age of onset. The disorder tends to be chronic, causes moderate levels of impairment in functioning and quality of life, and frequently is complicated by other Axis I and Axis II comorbid disorders. As a consequence, the focus of GAD treatment should be on long-term management strategies. This article summarizes available data on the longitudinal course of GAD, and provides a critical review of issues important to the long-term pharmacologic treatment of the disorder.

Long-term pharmacologic treatment of women with hypertension.

As reviewed in "Hypertension in Women: What is Really Known?" (Women's Caucus Working Group on Women's Health of the Society of General Internal Medicine [1991] Ann Intern Med 115:287-293), the published literature reveals that hypertension frequently occurs in women and that only some prospective studies have defined specific benefits and risks of long-term pharmacologic treatment. Major U.S. epidemiologic studies show the incidence of hypertension to very between 20% and 50% of the population. It is more common among Afro-Americans than White Americans. Frequency increases with aging. Several studies of at least 3 years duration that have focused on the use of diuretics and B blockers are reviewed: Hypertension Detection and Follow-Up Program (HDFP), Medical Research Council (MRC), MRC trial in the treatment of older adults (MRC-Older), and isolated systolic hypertension in the elderly (SHEP). Both diuretics and B blockers generally lower blood pressure, and decrease stroke incidence and mortality. Diuretics seem to be more effective and better tolerated than B blockers. Long-term studies of newer antihypertensive agents do not yet exist. The sexual side effects of drugs have only been studied to a limited degree in women. © 1995 Wiley-Liss, Inc.

Long-Term Pharmacologic Treatment of Panic Disorder

Acute and follow-up studies of these pharmacotherapeutic agents suggest that many patients, though improved, remain symptomatic despite treatment.

Phases of treatment: a practical approach to methadone maintenance treatment.

There has been an on-going controversy in the United States as to whether methadone should be used in the treatment of opiate addiction as a long-term pharmacological treatment or as a short-term medical intervention to help addicts attain an opiate-free state. This article describes a practical treatment approach which resolves this dichotomy and presents a clinical framework for the variable use of methadone to effectively meet the needs of each individual patient. The therapeutic process is highly structured and is divided into several phases of treatment for opiate addiction. The article describes each of these phases and illustrates how they can be translated into clinical/medical practice. Some of the issues regarding medical maintenance, as well as methadone tapering and maintaining subsequent abstinence, are also addressed.

Effects of hydrochlorothiazide, amiloride, and lisinopril on the metabolic, hemodynamic, and electrocardiographs responses to increased plasma epinephrine

I n the treatment of cardiovascular disease, such as hypertension and heart failure, minor metabolic side effects of the long-term pharmacologic treatment might be of importance. Thus, diuretics may jnduce a potentially’arrhythmogenic hypokalemial and have negative effects on the glucose metabolism, and both diuretics and l3 blockers may have adverse effects on blood lipid levels2 that might increase the risk of coronary artery disease, despite the benefits provided by these drugs’ antihypertensive actions. In experimental settings, an infusion of epinephrine given at a rate to obtain serum concentrations comparable to those seen in acute myocardial infarction has profound metabolic and electrocardiographic effects that are known to facilitate the development of malignant ventricular arrhythmias.3 These effects of epinephrine may be aggravated by some drugs commonly prescribed in cardiovascular disorders.” This study investigated the effects of pretreatment with hydrochlorothiazide, amiloride, and lisinopril on the response to an epinephrine infusion. were analyzed: potassium, magnesium, calcium, phosphate, urate, albumin, creatinine, and blood glucose. An electrocardiographic recording was made during the infusion and for the following 30 minutes. The recordjng was analyzed for heart rate, T-wave amplitude, QRS duration, and QT interval. Systolic and diastolic (phase V) blood pressures were also determined. Prior to the epinephrine infusion, the volunteers were pretreated in random order for 14 days with: (1) placebo, (2) hydrochlorothiazide (HCTZ) 50 mg daily, (3) amiloride 10 mg daily, and (4) lisinopril 20 mg daily. Each volunteer received all of the pretreatments (Latin square design). The results were expressed as mean +: standard deviation. For statistical analysis, a multivariate analysis of variance for repeated measurements (MANOVA) was used with time during epinephrine infusion and the various pretreatments as within-subject factors.

Mechanisms of action in cognitive-behavioral and pharmacological interventions for obesity and bulimia nervosa.

In the treatment of obesity, anorexiant medication appears to enhance restraint, presumably through altering internal cues, and facilitates weight loss with behavioral treatment. However, relapse occurs once medication is withdrawn. Antidepressants appear to work similarly, and initial evidence suggests the same limitations. Long-term combined pharmacologic and behavioral treatment, however, may be useful for some individuals not responding positively to behavioral treatment alone. In the treatment of bulimia nervosa, antidepressants appear to enhance restraint, whereas cognitive behavioral treatment decreases restraint. Thus, these modalities appear to be incompatible, and highly restrictive eating is not desirable for those of normal weight. However, for individuals not responding to cognitive-behavioral treatment, long-term pharmacologic treatment may be an alternative, perhaps combined with a more compatible psychological treatment.

Mechanisms of action in cognitive-behavioral and pharmacological interventions for obesity and bulimia nervosa.

In the treatment of obesity, anorexiant medication appears to enhance restraint, presumably through altering internal cues, and facilitates weight loss with behavioral treatment. However, relapse occurs once medication is withdrawn. Antidepressants appear to work similarly, and initial evidence suggests the same limitations. Long-term combined pharmacologic and behavioral treatment, however, may be useful for some individuals not responding positively to behavioral treatment alone. In the treatment of bulimia nervosa, antidepressants appear to enhance restraint, whereas cognitive behavioral treatment decreases restraint. Thus, these modalities appear to be incompatible, and highly restrictive eating is not desirable for those of normal weight. However, for individuals not responding to cognitive-behavioral treatment, long-term pharmacologic treatment may be an alternative, perhaps combined with a more compatible psychological treatment.

Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar I illness: a naturalistic study

The authors conducted an 18-month naturalistic prospective follow-up study of 37 adolescents whose bipolar I illness had been stabilized with lithium carbonate during inpatient hospitalization. Thirteen of the patients discontinued prophylactic lithium therapy shortly after discharge. The relapse rate of bipolar illness in these 13 patients was nearly three times higher than the rate in patients who continued lithium prophylaxis without interruption. Early relapse among lithium-treated patients was associated with a greater risk of relapsing again. The authors discuss the theoretical and clinical implications of these findings.

Correlation of severity of panic disorder and neuroanatomical changes on magnetic resonance imaging

Thirty consecutive lactate-sensitive panic disorder patients were studied with magnetic resonance imaging (MRI) to investigate the relationship between temporal lobe abnormalities and panic disorder. Neuroanatomical abnormalities, most involving the right temporal lobe, were found in 43% of patients, compared with 10% of the control subjects. Patients with temporal lobe abnormalities were significantly younger at the onset of panic disorder and had more panic attacks compared with patients with normal MRI scans (p less than .05). These results suggest that panic disorder could be secondary to temporal lobe dysfunctions and that panic disorder patients with abnormal MRIs could have a worse prognosis than those with normal MRIs and would require long-term pharmacological treatment.

Stereotactic amygdalotomy in the light of neuropsychological investigations.

The aim of this paper is to describe on the basis of comparative psychological studies the effect of partial amygdalectomy on the behaviour and cognitive processes of patients with acute forms of epilepsy whose long-term pharmacological treatment, and in some cases also conventional surgical treatment, had been unsuccessful.