Showing papers in "The Journal of Clinical Psychiatry in 1993"

The economic burden of depression in 1990.

Abstract: Background We estimate in dollar terms the economic burden of depression in the United States on an annual basis. Method Using a human capital approach, we develop prevalence-based estimates of three major cost-of-illness categories: (1) direct costs of medical, psychiatric, and pharmacologic care; (2) mortality costs arising from depression-related suicides; and (3) morbidity costs associated with depression in the workplace. With respect to the latter category, we extend traditional cost-of-illness research to include not only the costs arising from excess absenteeism of depressed workers, but also the reductions in their productive capacity while at work during episodes of the illness. Results We estimate that the annual costs of depression in the United States total approximately $43.7 billion. Of this total, $12.4 billion-28%-is attributable to direct costs, $7.5 billion-17%-comprises mortality costs, and $23.8 billion-55%-is derived from the two morbidity cost categories. Conclusion Depression imposes significant annual costs on society. Because there are many important categories of cost that have yet to be estimated, the true burden of this illness may be even greater than is implied by our estimate. Future research on the total costs of depression may include attention to the comorbidity costs of this illness with a variety of other diseases, reductions in the quality of life experienced by sufferers, and added out-of-pocket costs resulting from the effects of this illness, including those related to household services. Finally, it may be useful to estimate the additional costs associated with expanding the definition of depression to include individuals who suffer from only some of the symptoms of this illness.

Pharmacokinetics of antidepressants: Why and how they are relevant to treatment.

Abstract: The pharmacokinetics of antidepressants are reviewed with special emphasis on clinical applicability. There are substantial pharmacokinetic differences among the five major classes. Pharmacokinetic differences between members of a specific class are usually modest except for serotonin selective reuptake inhibitors. Between members of this class pharmacokinetic differences are the major distinguishing variables and have clinically important consequences.

Obsessive compulsive disorder with psychotic features.

Abstract: Background The purpose of this study was to systematically identify and characterize the demographic and clinical features of patients with obsessive compulsive disorder (OCD) and psychotic symptoms. Methods From a total of 475 patients with DSM-III-R OCD evaluated and/or treated in an outpatient OCD clinic, 67 patients (14%) were identified as having psychotic symptoms in addition to OCD. Psychotic symptoms were defined as hallucinations, delusions, and/or thought disorder. Clinical and demographic data on these probands were collected from semistructured interviews and compared with data collected on the nonpsychotic OCD probands. Results We identified 27 (6%) of 475 probands with DSM-III-R OCD whose only psychotic symptom was lack of insight and high conviction about the reasonableness of the obsessions ("OCD without insight"). The remainder of the patients with psychotic symptoms and OCD met criteria for distinct DSM-III-R psychotic disorders as well as OCD: 18 probands (4%) had OCD and schizophrenia, 8 probands (2%) had OCD and delusional disorder. Fourteen patients (3%) met criteria for both OCD and schizotypal personality disorder. Compared with the OCD patients without psychosis, probands with OCD and psychotic features were more likely to be male, be single, have a deteriorative course, and have had their first professional contact at a younger age. The data suggest that these differences were largely due to those patients with OCD and schizophrenia-spectrum disorders and not those probands whose only psychotic symptom was complete conviction and lack of insight about their obsessions. Conclusion There appears to be considerable heterogeneity in the clinical features of OCD patients who also have psychotic symptoms. The implications of these findings for understanding delusional states and for diagnostic classification are discussed.

Seizures associated with antidepressants: A review

Abstract: Background Seizures are uncommon, but serious, adverse effects of antidepressant drugs. A better understanding of drug-related seizure risk, its predictors, and its neurophysiologic basis might help clinicians avoid this adverse event. A better understanding of the factors involved in the determination of seizure risk would be helpful for interpretation of seizure rates reported. Method The authors review case reports, series of cases, and information from clinical trials of antidepressants to determine antidepressant-related seizure risk. Predisposing factors are identified. Effects of dose, blood levels, and duration of treatment on seizure risk are examined. Electrophysiologic and in vitro models of drug-related seizure induction are discussed. Results A significant proportion of drug-related seizures occurs in individuals with an identifiable predisposition, such as previous seizures, sedative or alcohol withdrawal, and multiple concomitant medications. Seizure risk for most antidepressants increases with dose (or blood level), and comparisons between drugs should consider seizure rates at the effective dose (or blood level) for each drug. For imipramine, the most frequently studied tricyclic, the literature indicates a seizure rate between 0.3% and 0.6% at effective doses. In unselected patients and at higher doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone, nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk. Estimates for recently marketed antidepressants with intermediate seizure risk are complicated by the fact that effective doses and blood levels are not well established. Conclusion Assessment of seizure risk in individuals involves consideration of predisposing factors, the antidepressant selected, and the bioavailability of the drug. Future studies of seizure risk would benefit from the use of specified criteria for determination of probable seizure events, a priori definition of predisposing exclusions, samples sufficiently large to provide adequate power, blood level monitoring, and inclusion of duration of drug treatment in the calculation of risk.

Depression: a neglected major illness.

Abstract: BACKGROUND: To illustrate the burden depression imposes on society, we present estimates of the annual costs of depression--$44 billion--as well as the number of individuals it affects per year--almost 11 million. Although these estimates point to depression as a major illness, this study examines why it is not generally considered as such by the medical and public health communities or by society at large. METHOD: We develop a framework that compares depression with major illnesses such as coronary heart disease, cancer, and AIDS by highlighting salient characteristics of each illness. This comparative illness framework considers the costs, prevalence, distribution of sufferers, mortality, recognition, and treatability of each disease. This comparison underscores many of the similarities and differences among the illnesses examined. RESULTS: Because depression often is not properly recognized and begins to affect many people at a relatively early age, it exacts costs over a longer period of time and in a more subtle manner than other major illnesses. It also imposes a particularly heavy burden on employers in the form of higher workplace costs. CONCLUSION: We conclude that, because of the potential for successful treatment, increased attempts to reach untreated sufferers of depression appear to be warranted. Employers as a group have a particular incentive to invest in the recognition and treatment of this widespread problem, in order to reduce the substantial costs it imposes upon them each year. Language: en

SPECT and PET imaging in mood disorders.

Abstract: Single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies are yielding a picture of clinical depression as a disorder associated with dysfunction in specific brain regions. These data support the view of depression as a disease of the brain in general and of the frontal and temporal lobes in particular. Frontal lobe hypometabolism is emerging as a common final pathway for most types of primary and secondary depression, regardless of the original cause. The severity of depression is often related to the degree of frontal hypometabolism, and preliminary studies indicate that the hypometabolism normalizes after treatment in concert with the patient's improved mood. Primary depression also is associated with abnormal activation of key brain areas, including discrete aspects of the frontal and temporal lobes, the amygdala, and the cingulate gyrus. Several areas of research are currently under way using SPECT or PET to explore further the neuroanatomy of depression.

Sexual dysfunction during antidepressant treatment.

Abstract: Background The reported incidence of sexual dysfunction associated with antidepressant medication varies from 1.9% to 92%. The majority of studies reporting incidences were not systematically conducted. Method We interviewed 60 patients (22 men and 38 women, with anxiety and mood disorders) who were being treated with various antidepressants. We used a questionnaire focused on sexual side effects and other side effects. Results The incidence of sexual dysfunction during antidepressant use in our study is 43.3%. The sexual dysfunction was not limited to any particular diagnostic group nor to any particular antidepressant. There was no significant correlation between sexual dysfunction and anticholinergic side effects. The incidence of painful orgasm with antidepressants was 18% among males in our study. Conclusion The relatively high incidence of sexual dysfunction associated with antidepressant treatment in this systematic study emphasizes the importance of a detailed inquiry about sexual side effects as this interferes with treatment compliance.

Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion.

Abstract: Background This study was conducted to determine the effect of bupropion on the sexual functioning of male and female outpatients who developed anorgasmia or delayed orgasm while receiving fluoxetine treatment for depression Method Thirty-nine patients who satisfied criteria for participation in the study discontinued fluoxetine treatment and entered a 2-week washout phase followed by an open 8-week bupropion treatment phase Three parameters of sexual functioning were followed throughout the study: orgasm function, libido, and satisfaction with overall sexual functioning Depression was also evaluated at each visit Results All patients reported orgasm delay and/or failure at the time of fluoxetine discontinuation Orgasm function, libido, and satisfaction with sexual functioning improved during the 2-week fluoxetine washout period and during the bupropion treatment phase Ninety-four percent of patients (29/31) had complete or partial resolution of their orgasm dysfunction at the end of bupropion treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied with their overall sexual functioning Most patients entered the study with decreased libido on fluoxetine Libido was "much" or "very much" increased for 81% of patients (25/31) at the end of the study In addition, depression scores on the Hamilton Rating Scale for Depression and Clinical Global Impressions-Severity scale significantly improved during the bupropion treatment phase Finally, bupropion was well tolerated by most patients Conclusion Bupropion may be an appropriate antidepressant for patients who develop sexual dysfunction during fluoxetine treatment or for whom sexual dysfunction is a concern

Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment.

Abstract: Background Many studies of thyroid augmentation in refractory depression are methodologically weak, have had mixed results, and often do not include biological measures of hormonal effects. In this paper, recent clinical and preclinical research on thyroid dysfunction in refractory depression is reviewed. Method A search of MEDLINE for articles published from 1970 to the present was conducted, in addition to a search of the bibliographies of published papers in this area. The clinical studies chosen for review included those in which the patient population was identified as having refractory depression and where a specific measure of thyroid function was used, such as thyroid indices, thyroid-releasing hormone stimulation, or basal metabolic rate. Animal studies of depression using the learned helplessness experimental paradigm were also reviewed and included if they examined the factors involved in antidepressant treatment response. Results Fifty-two percent of patients with refractory depression in six clinical studies evidenced subclinical hypothyroidism (range, 29%-100%), which can be contrasted with a prevalence of approximately 8% to 17% in unselected populations of depressed patients. Four studies investigating an animal model of refractory depression strongly implicate a pathophysiologic role for hypothyroidism, perhaps mediated by altered beta-adrenergic function. Conclusion These findings indicate that hypothyroidism is significantly associated with refractory depression, suggesting that this characterizes one biological subtype of refractory depression. Failure to rigorously investigate the effects of thyroid augmentation, including measures of thyroid and beta-adrenergic function, may partly explain the ambiguous results from many treatment studies, and future research should incorporate these measures in the study of refractory depression.

Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications.

Abstract: BACKGROUND Tardive dyskinesia (TD) has been a source of great concern to the psychiatric community because of the iatrogenic nature of the illness. Little is known about the risk of developing TD if neuroleptic medications are continued. METHOD This paper presents long-term risk estimates for TD in a prospective cohort study of 362 chronic psychiatric outpatients who were free of TD at baseline and who were maintained on neuroleptic medications. RESULTS On the basis of 5 years of follow-up, we estimate the risk of persistent TD to be 32% after 5 years of neuroleptic exposure (95% confidence interval [CI] = 23%-43%), 57% after 15 years of exposure (95% CI = 47%-66%), and 68% after 25 years of exposure (95% CI = 58%-77%). For patients with 10 years of previous neuroleptic exposure, the risk is 15% after 5 more years of exposure (95% CI = 7.2%-27%) and 38% after 15 more years of exposure (95% CI = 24%-53%). Our results fall within the wide range of results found in other studies of TD incidence. Differences in incidence across studies may be explained in terms of patient characteristics and other methodological factors. CONCLUSION One implication of this finding is that patients in the first 5 years of exposure could be targeted for prevention programs if resources are limited. A potential methodological problem encountered when studying chronically exposed patients is that they may have acquired TD (persistent) prior to the study and remitted before entry.

Fluoxetine efficacy in social phobia.

Abstract: BACKGROUND To determine the efficacy of fluoxetine in the treatment of social phobia, fluoxetine was administered to 16 patients with a primary DSM-III-R diagnosis of social phobia in a 12-week, open, clinical trial. METHOD Treatment began at 20 mg of fluoxetine daily and was increased according to clinical response and side effects every 4 weeks. Patients completed self-report measures of anxiety and depression at baseline and at Weeks 4, 8, and 12. These included the Beck Depression Inventory, the Social Avoidance and Distress Scale, the Fear of Negative Evaluation Scale, the State-Trait Anxiety Inventory, the Fear Questionnaire, the Social Anxiety Thoughts Questionnaire, and the Social Adjustment Scale-Self-Report. Clinicians completed a Clinical Global Improvement Scale. RESULTS Thirteen of the 16 patients completed the trial. Three patients (18.8%) were unable to complete the trial due to adverse side effects. Of the 13 (81.2%) remaining patients, 10 were considered to be responders and 3 were considered to be nonresponders. Measures of social anxiety and phobic avoidance showed a significant improvement from baseline to endpoint, achieving a significance of p < .005. Responders to fluoxetine were more likely to have been older at onset of the social phobic symptoms and had a shorter duration of illness. CONCLUSION These findings suggest that fluoxetine may be effective in the treatment of social phobia. Double-blind studies will be required to further investigate these findings.

SSRI-associated nocturnal bruxism in four patients.

Abstract: Background Nocturnal bruxism (tooth clenching and/or grinding during sleep) affects a significant proportion of the population. Its etiology remains uncertain, and no entirely satisfactory treatment is available. Method This is an observational report of four depressed individuals selected from one psychiatrist's practice within an urban hospital's psychopharmacology clinic. Psychiatric diagnoses were made according to DSM-III-R criteria. Nocturnal bruxism was determined on the basis of dental examination and/or self-reported nocturnal tooth clenching and/or grinding. Results Four patients developed nocturnal bruxism within 2 to 4 weeks after initiation of treatment with fluoxetine or sertraline. Bruxism remitted in all patients after a decrease in antidepressant dosage (N = 1) or addition of buspirone (N = 3). Conclusion These observations, which should be confirmed by a controlled study, suggest an association between serotonin selective reuptake inhibitor (SSRI) treatment and the onset or exacerbation of nocturnal bruxism. In addition, they suggest that a decrease in SSRI dosage or the addition of buspirone may relieve SSRI-associated nocturnal bruxism.

Does clozapine cause tardive dyskinesia

Abstract: Background The authors attempted to determine if chronic exposure to clozapine can cause tardive dyskinesia. Method Twenty-eight schizophrenic or schizoaffective patients with no prior history of definite tardive dyskinesia were treated with clozapine for at least 1 year, and their ongoing modified Simpson Dyskinesia Scale ratings were analyzed. These data were then compared with those of another group of similarly diagnosed patients who were treated with a conventional neuroleptic for at least 1 year. Results Two patients in the clozapine-treated group (both of whom had ratings of questionable tardive dyskinesia at baseline) were later rated by the modified Simpson Dyskinesia Scale as having mild tardive dyskinesia on at least two consecutive ratings 3 months apart. Although there was uncertainty about whether clozapine definitely caused the tardive dyskinesia in those two patients, a survival analysis comparing the clozapine-treated group with the neuroleptic-treated group showed a lower risk of tardive dyskinesia developing in the clozapine-treated group. Conclusion This study was unable to definitively conclude whether clozapine causes tardive dyskinesia. However, if cases do develop, the risk of tardive dyskinesia is likely to be less with clozapine than with typical neuroleptics.

Valproate oral loading in the treatment of acute mania.

Abstract: Background Evidence from earlier studies suggests that the antimanic activity of valproate becomes most pronounced within 1 to 4 days of achieving serum concentrations of 50 mg/L or greater. We conducted a prospective study to assess the onset of antimanic activity of oral loading dosages of valproate administered to achieve serum concentrations above 50 mg/L within 24 hours. Method Nineteen patients with bipolar disorder, manic phase, received divalproex sodium 20 mg/kg/day in divided dosages for 5 days, without other psychotropic agents except lorazepam up to 4 mg/day. Serum valproate concentrations were measured after 1 and 4 days of treatment. Improvement was measured daily by a blind rater using the Young Mania Rating Scale (MRS). Results Serum valproate concentrations greater than 50 mg/L were reached in all 15 patients completing the study. Ten (53%) of the 19 patients who received at least one complete loading dose displayed a significant (greater than 50%) reduction in MRS scores by study termination. These responders displayed the greatest percent change in MRS scores over the first 3 days of treatment. Side effects were minimal. Conclusion Valproate can be safely administered by oral loading and may produce rapid onset of antimanic response in some patients.

Postpartum obsessive compulsive disorder: a case series.

Abstract: Background The puerperium has typically been a period of risk for the development of psychiatric illness. Although postpartum depressive illness has been discussed extensively in the literature, obsessive compulsive disorder during pregnancy and puerperium has received little attention. Method Fifteen women with new-onset obsessive compulsive symptoms during the puerperium were retrospectively evaluated by chart review; all met DSM-III-R criteria for obsessive compulsive disorder. Distinctive features of their clinical presentation, pharmacotherapy received, and status at 1-year follow-up were recorded. Results Patients were noted to have a characteristic constellation of symptoms comprised of disabling intrusive obsessional thoughts to harm their babies. Obsessive rituals were not observed in any of the patients described. Patients frequently developed secondary depression and appeared to be exquisitely responsive to serotonin selective reuptake inhibitors. Conclusion The puerperium may be a period of risk for development of new-onset obsessive compulsive disorder. Clinicians caring for puerperal women need to be aware of the impact of these symptoms on maternal and fetal well-being.

The effects of race and comorbidity on clinical diagnosis in patients with psychosis.

Abstract: Background For several years, studies have indicated that schizophrenia is overdiagnosed in nonwhite patients with psychosis. Whether these reports have altered racial diagnostic patterns in clinical settings remains uncertain. We hypothesized that the clinical overdiagnosis of schizophrenia in nonwhite patients persists in the public sector. Further, we explored whether differences between races in secondary (comorbid) diagnoses contribute to discrepancies in primary diagnoses. Method Data were obtained by retrospective chart reviews of 173 patients with psychotic disorders discharged during a recent 7-month period from a large state psychiatric hospital. Demographic and clinical variables were obtained from the medical records. All clinical information had been recorded by the treatment teams without knowledge of this study. Only black and white racial subgroups were represented in this sample. Results Black patients were significantly more likely to be diagnosed with schizophrenia than white patients (odds ratio = 5.1), and men were more likely to be diagnosed with schizophrenia than women (odds ratio = 1.9). This racial pattern was observed even in the subgroup of patients hospitalized for the first time (odds ratio = 7.0). Neither the type nor frequency of comorbid diagnoses significantly differed between races. Additionally, black patients received higher doses of antipsychotic medication. Conclusion Black patients with psychosis are significantly more likely to be diagnosed with schizophrenia than similar white patients in the public sector. This may reflect underdiagnosis of affective illness in black patients. Additionally the higher doses of antipsychotic medication that black patients received may alter clinical presentation and contribute to this discrepancy in diagnosis.

Dose response of prophylactic antipsychotics

Abstract: A review of the literature concerning the use of oral and depot antipsychotic medication has high-lighted some important considerations in the treatment of chronic schizophrenic patients. All patients not treated with any form of antipsychotic drug will relapse within 3 years. These relapses will be more clinically significant and will occur at greater frequency than in patients who receive medication on a regular basis. Careful consideration should be given to each patient when choosing between oral or depot medication and inpatient or outpatient therapy. In addition, the clinician should consider the dosage schedule of each medication and balance this against the probability of extrapyramidal side effects and noncompliance. One option for the prevention of relapse without an increase in adverse side effects is the administration of depot haloperidol. For all therapeutic options, medication should be given on a regular basis, since intermittent dosing strategies do not work, and psychosocial rehabilitation should be initiated.

Alcohol, drugs, and psychiatric comorbidity among homeless women: an epidemiologic study

Abstract: Background Very little is known about the mental health of homeless women. The present study is one of the first to focus on psychiatric diagnosis and comorbidity in a population of homeless women systematically interviewed with a structured instrument. Method Three hundred homeless women randomly selected from St. Louis shelters were interviewed using the Diagnostic Interview Schedule (DIS). Results The population of homeless women in St. Louis is predominantly young adult, single, and black; most have young children and average nearly a high school education. Schizophrenia and bipolar affective disorder account for only a small portion of the mental illness in these women. Nearly one in three has a history of substance abuse, with drug abuse being more prevalent than alcoholism. One third of the sample met lifetime criteria for posttraumatic stress disorder. One fourth of the women have received inpatient psychiatric care, and the majority with a nonsubstance Axis I diagnosis have received some mental health treatment. Conclusion Although major mental illness is overrepresented among these homeless women, the majority do not suffer from major mental illness. Despite the severity of the stressors these women face, the large numbers escaping psychiatric disorders speak to their resilience and to the likelihood that important factors other than mental illness contribute to their homelessness. Future studies to examine positive outcomes and investigate protective factors might provide a valuable source of information on coping with the stresses associated with homelessness and point to more effective interventions.

An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression.

Abstract: Background: We evaluated the efficacy of buspirone in the augmentation of antidepressant response to the serotonin reuptake inhibitors, Method: Twenty-five patients with major depressive disorder who had failed several previous treatments for their current depressive episode were included. After failing a trial of fluoxetine or fluvoxamine, they received buspirone in addition to the serotonin reuptake inhibitor for 3 weeks in an open clinical trial, Results: Seventeen of 25 patients had a marked or complete antidepressant response, Conclusion: These data provide clinical evidence suggesting that buspirone augmentation may be a useful clinical alternative in depressed patients who fail to respond to a serotonin reuptake inhibitor

Obsessive compulsive disorder in children and adolescents: issues in management.

Abstract: Clinical experience with children and adolescents with obsessive compulsive disorder (OCD) suggests the need for long-term care. In addition to maintenance drug treatment, behavior therapy and family counseling are usually indicated. Family counseling can help prevent the avoidant behavior that is a serious complication of OCD. The outcome for OCD in children and adolescents has been improved by the use of these active long-term therapies

Psychotropic Treatment of Chronic Fatigue Syndrome and Related Disorders

Abstract: BACKGROUND Chronic fatigue syndrome (CFS) and fibromyalgia frequently are associated with symptoms of major depression For this reason, antidepressants have been used in treatment of these disorders; however, little direction has been provided into this application in psychopharmacology METHOD First, nine studies were reviewed regarding the relationship of the symptoms of fatigue and depression Next, 23 reports (12 double-blind studies, 7 open studies, and 4 case reports) were reviewed for the effectiveness of therapy as assessed by global response and improvement of both depression and pain Studies were differentiated by type of controls, as well as by alleged mechanism of action of the pharmacologic agent RESULTS Disturbances in brain neurochemistry shared by CFS and major depression may serve as a basis for the effectiveness of some antidepressants in CFS Response to some antidepressants in patients with CFS or fibromyalgia may occur at doses lower than those used in major depression, eg, amitriptyline 25-75 mg/day We further found that the more serotonergic treatments (eg, clomipramine) were more successful in alleviating pain than depression, whereas catecholaminergic agents (eg, maprotiline, bupropion) seemed particularly effective for symptoms of associated depression CONCLUSION To maximize response of the physiologic and psychological consequences of the disorder, more investigation is needed to replicate the apparent findings that relate the neurochemical impairment underlying CFS and fibromyalgia to the type of antidepressant mechanism

Low-dose valproate: a new treatment for cyclothymia, mild rapid cycling disorders, and premenstrual syndrome

Abstract: Background Valproate has proved useful in the treatment of manic-depressive and schizoaffective disorders, usually in daily doses above 500 mg with corresponding blood levels in the range established for treatment of epilepsy (50-100 micrograms/mL). Since milder bipolar disorders may be more prevalent than bipolar I disorder, a prospective study was undertaken to determine whether lower doses of valproate might be useful for stabilization of mood cycling in patients having primary diagnoses of cyclothymia or rapid cycling bipolar II disorder. Additionally, open trials of low-dose valproate were conducted in a small number of women complaining of premenstrual syndrome. Method Over a 3-year period, outpatients with non-menstrually-related rapid cycling who had fulfilled DSM-III-R criteria for cyclothymia or bipolar II disorder were started on open trials of valproate at daily doses of 125 or 250 mg. Doses were adjusted upward on approximately a monthly basis depending upon clinical response, and valproate blood levels were obtained. Results Twenty-six (79%) of 33 patients (15 cyclothymics, 11 bipolar II) reported sustained partial or complete stabilization of mood cycling with valproate doses ranging from 125 to 500 mg (mean = 351.0 mg) corresponding to serum valproate levels (mean = 32.5 micrograms/mL) substantially below the current recommended range. Cyclothymics required significantly lower doses and blood levels of valproate than patients with bipolar II disorder for stabilization of mood. Five patients (all bipolar II) failed to respond fully to low doses of valproate but improved with higher doses corresponding to blood levels in the 50 to 100 micrograms/mL range. Two patients had poor responses to valproate or intolerable side effects. In contrast to bipolar spectrum patients, only three (38%) of eight women with menstrually related cycling of mood reported good responses to low doses of valproate, while five reported no response to valproate. Conclusion The findings suggest that (1) low-dose valproate may be useful in the treatment of cyclothymia and milder rapid cycling bipolar disorders and (2) there may be a correlation between the severity of bipolar disorder and the blood level of valproate required for stabilization such that milder forms of bipolar cycling require lower doses of valproate.

Biological approaches to treatment-resistant obsessive compulsive disorder.

Abstract: Biological approaches to the patient with treatment-resistant obsessive compulsive disorder are briefly reviewed. The most commonly employed strategy involves combining a potent serotonin reuptake inhibitor (SRI) (e.g., clomipramine or fluvoxamine) with another medication that may exert effects on the brain serotonin system. Open-label reports regarding the addition of tryptophan, fenfluramine, lithium, or buspirone to ongoing SRI therapy of obsessive compulsive disorder are encouraging. However, the anti-obsessive compulsive efficacy of SRI-lithium and SRI-buspirone combination therapy has not been confirmed in recent controlled trials. Preliminary evidence suggests that addition of neuroleptic may benefit SRI-refractory obsessive compulsive disorder patients who have a comorbid chronic tic disorder. Other biological approaches (e.g., electroconvulsive therapy and psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant obsessive compulsive disorder. Finally, an algorithm is proposed for those patients with obsessive compulsive disorder who fail to respond to an adequate trial with a potent SRI.

Possible effects of smoke-free inpatient units on psychiatric diagnosis and treatment.

Abstract: Background The author undertook to review the effects of abstinence from smoking and how those effects might influence the diagnosis and treatment of psychiatric disorders when patients are required to temporarily refrain from smoking (e.g., on inpatient wards) or when patients decide to stop smoking permanently. Method Computerized data bases and reference lists of existing articles were searched for prior publications from three areas: (1) the association of smoking and psychiatric disorders, (2) the effects of nicotine withdrawal, and (3) the role of nicotine in psychiatric disorders. Results Withdrawal-induced increases in anxiety, depression, insomnia, irritability, restlessness, and weight and decreases in heart rate could affect the ability to evaluate alcohol/drug withdrawal, anxiety disorders, etc. Withdrawal effects could mimic medication side effects or increase the blood levels of several psychiatric medications. Whether these effects occur frequently or are of clinical magnitude has not been tested in studies of psychiatric patients. Conclusion Psychiatrists should consider the effects of abstinence from smoking when diagnosing and treating patients who enter smoke-free inpatient units or who stop smoking during outpatient treatment.

Utilization of behavioral methods in a multicenter anxiety disorders study.

Abstract: BACKGROUND There are abundant data to justify the use of behavioral methods in treating patients with anxiety disorders Yet there also is evidence that these methods have been underutilized in treating these patients In this study we examined a large sample of patients with anxiety disorders to determine the extent to which behavior therapy methods were used in their treatment METHOD As part of a multicenter longitudinal study of patients with anxiety disorders in New England, we analyzed data pertinent to the type of treatment received by 231 patients at nine study sites Study subjects received a battery of interview and self-report instruments administered by trained study interviewers at intake and at 6-month follow-up A Psychosocial Treatments Interview designed by study personnel and administered by study interviewers at 6 months after intake provided data as to types of psychosocial treatment received by study subjects RESULTS Behavioral methods were used less frequently than supportive psychotherapy medication, or psychodynamic psychotherapy Among behavioral treatments, relaxation and imaginal exposure were used more frequently than in vivo exposure Obsessive compulsive disorder and agoraphobia without panic were the diagnoses most likely to be treated behaviorally Behavioral methods were used more frequently in combination with other modalities than they were alone CONCLUSION When compared with previous studies, the frequency of utilization of behavioral methods appears to have increased moderately But our data are still consistent with a pattern of inappropriately low utilization of these effective treatment methods

Review of the cardiovascular effects of heterocyclic antidepressants

Abstract: We review the effects of heterocyclic antidepressant compounds on the cardiovascular system. It has been shown that tricyclic antidepressants (TCAs) slow intraventricular conduction, and this can be seen on a standard ECG as the increased QRS, PR, and QTc intervals. This prolonged conduction is dangerous to patients in two conditions. In overdose, delayed conduction may lead to a complete heart block or ventricular reentry arrhythmias. Either of these complications, or a combination of both, may lead to death. When treated with TCAs at therapeutic plasma levels, depressed patients with preexisting conduction disease, particularly bundle-branch block, are at higher risk to develop symptomatic A-V block than depressed patients free of conduction disorders. Clinically, the effects of TCAs on conduction does not differ significantly within the family of drugs. Who gets complications is much more a function of severity of the patient's preexisting cardiac condition. The most common cardiovascular effect of TCAs is orthostatic hypotension. Postural hypotension is more dangerous in elderly patients because it may lead to falls that cause serious physical injuries. Severe orthostatic hypotension is more likely to develop in depressed patients with left ventricular impairment and/or in patients taking other drugs like diuretics or vasodilators. Nortriptyline has been shown to cause significantly less serious postural blood pressure drops, an important difference between this drug and other TCAs. Another cardiovascular effect of TCAs is that they reduce ventricular arrhythmias. They share this property with Type 1A antiarrhythmic compounds, and a variety of Type 1 antiarrhythmics have recently been shown to increase mortality in postmyocardial infarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The comparative pharmacology of new antidepressants.

Abstract: This review attempts to critically assess the evidence regarding the relationship between the specificity of antidepressants in modulating different neurotransmitter systems and their therapeutic activity. Evidence from experimental and clinical studies suggests that all antidepressants and electroconvulsive shock therapy produce qualitatively similar adaptive changes in serotonergic, adrenergic, and possibly GABAergic and dopaminergic transmission following chronic treatment. Such adaptational changes parallel the onset of the therapeutic response. The relationship between the pharmacokinetics and the therapeutic efficacy and safety of the serotonin selective reuptake inhibitors (SSRIs) is considered with particular attention to fluoxetine, fluvoxamine, sertraline, and paroxetine. The primary difference between these drugs lies in their half-lives; fluoxetine and its major active metabolite norfluoxetine have a combined half-life exceeding 7 days. All the SSRIs are well tolerated with a low incidence of life-threatening side effects. Nausea and, rarely, vomiting occur quite frequently as a consequence of increased serotonergic activity in the gastrointestinal tract and possibly via central 5-HT3 receptors. The safety and prolonged efficacy of the SSRIs render them particularly beneficial for the long-term treatment of the depressed patient. Evidence is provided that, in order to prevent relapse, depressed patients should be maintained on continuous antidepressant therapy for at least 1 year, and at the same dose as that required to treat the acute phase of the illness. The review concludes with a brief summary of the therapeutic use of the SSRIs in the treatment of panic attack, obsessive compulsive disorder, and bulimia with a brief comment on the different subtypes of serotonin receptors that may be involved.

The effects of clozapine on severely aggressive psychiatric inpatients in a state hospital.

Abstract: BACKGROUND After noting a dramatic reduction in aggression and agitation in five psychotic inpatients residing on a specialized unit for the severely aggressive, the authors conducted a retrospective chart review to assess the possible role of clozapine treatment in this change METHOD The authors culled 12 months of nursing data, including progress notes, orders for seclusion, and mechanical and chemical restraint, to tabulate the frequency of aggression before and after the initiation of clozapine treatment, and looked at ratings on the Brief Psychiatric Rating Scale and periodic review reports to assess overall clinical change RESULTS The results of the review indicate that although psychotic symptoms were not greatly affected by the drug, the overall frequency of assaults, self-abuse, and the use of seclusion, mechanical restraint, and chemical restraint was reduced in the subjects CONCLUSION The authors conclude that because the reduction of aggression and agitation coincided with clozapine treatment, it is likely that clozapine was responsible for the change The authors propose possible reasons for this effect and suggest that controlled studies are needed to substantiate these preliminary results

Comorbidity and mixed anxiety-depressive disorders: is there epidemiologic evidence?

Abstract: Recent epidemiologic studies (i.e., studies conducted since 1980) have consistently demonstrated, on the basis of standardized diagnostic assessments, that there is a substantial overlap between different types of anxiety and depressive disorders. The current literature, however, discusses this issue primarily within the concept of comorbidity and there are some controversies about the existence of a separate disorder of mixed anxiety-depression (MAD). MAD can be defined by the presence of mixed symptoms of depression and anxiety that are below the diagnostic threshold for either one of these diagnoses. Since MAD has not been included in any of the current official classification systems, its prevalence, risk factors, course, and outcome have not been studied specifically in any of the recent epidemiologic studies even though MAD is thought to be very important, especially in primary care settings. This paper reviews recent epidemiologic studies and presents data from the Munich Follow-Up Study, which has found a prevalence of about 1% for MAD as defined by the ICD-10. Despite the lack of clear diagnostic criteria for MAD, there are some indications that: (1) this disorder might be frequent in primary care settings, and (2) patients with MAD frequently demonstrate subjective suffering, show impairment in personal and occupational functioning, and have high health service utilization rates. Current empirical evidence is still insufficient for deciding a suitable classificatory solution for this problem.