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Showing papers in "Annals of Clinical Psychiatry in 2003"


Journal ArticleDOI
TL;DR: The history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine are covered, which have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism.
Abstract: Clozapine (Clozaril®) is a novel and unique prototype atypical, tricyclic, dibenzodiazepine-derivative, antipsychotic agent. It has been proven effective and significantly superior to placebo, as well as to conventional neuroleptics, in several placebo-controlled, double-blind studies in treatment-resistant schizophrenia. It has also been found to produce an incidence of extrapyramidal symptoms (EPS) as low as that found with placebo. Approximately 30–60% of all schizophrenic patients who fail to respond to typical antipsychotics may respond to clozapine. It was the first major advance that marked a turning point in the treatment of schizophrenia and other psychotic disorders since the introduction of the typical antipsychotic agents, i.e., chlorpromazine and haloperidol in the 1950s and 1960s, respectively. After its introduction in clinical studies in the United States in the early 1970s, it was withdrawn in 1974, and was not approved for clinical use in the United States until February 1990, because of the risk of agranulocytosis. Its novel pharmacological profile, lack of propensity to cause EPS in both short- and long-term uses, lack of effects on serum prolactin, and ameliorative effects on tardive dyskinesia have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism. This review covers the history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine.

174 citations


Journal ArticleDOI
TL;DR: This article assessed indirect interpersonal exposure to the 1995 Oklahoma City bombing, broadcast and print media exposure in the aftermath of the explosion, emotional reactions to media coverage, and posttraumatic stress reactions in children distant from the explosion.
Abstract: This study assessed indirect interpersonal exposure to the 1995 Oklahoma City bombing, broadcast and print media exposure in the aftermath of the explosion, emotional reactions to media coverage, and posttraumatic stress reactions in children distant from the explosion. A survey was administered to 88 sixth-grade students in the public middle school in a community 100 miles from Oklahoma City 2 years after the bombing. Many children reported indirect interpersonal exposure and most reported bomb-related media exposure. Print media exposure was more strongly associated with enduring posttraumatic stress than broadcast exposure. Indirect interpersonal exposure and the interaction of media exposure with emotional reaction to media coverage in the aftermath of the explosion each predicted ongoing posttraumatic stress. The results suggest that children may have lingering reactions to highly publicized terrorist incidents. Concern about the influence of television viewing has long been proclaimed. This study implicates print media exposure as well. Media exposure to terrorist incidents, therefore, should be monitored and those working with children should assess exposure and stress even in children not directly impacted.

118 citations


Journal ArticleDOI
TL;DR: Five patients with delusional parasitosis were treated with atypical antipsychotic agents with favorable results, and the role of serotonin/dopamine antagonists and the possible role of serotonergic antidepressants in the treatment of these patients were reviewed.
Abstract: Delusional parasitosis is the false belief that one's body is infested with one or many different living organisms. Historically, it has been treated with conventional antipsychotics with only moderate success. The conventional antipsychotic most commonly used has been pimozide. We report a series of five cases of patients with delusional parasitosis. Our patients' demographic characteristics were similar to those in previously published case reports, but instead of being treated with older antipsychotics, they were all treated with atypical antipsychotic agents with favorable results. We will discuss the rationale for this treatment choice, and will review the role of serotonin/dopamine antagonists in the treatment of delusional parasitosis. We will also comment on the possible role of serotonergic antidepressants in the treatment of these patients.

56 citations


Journal ArticleDOI
TL;DR: The categorical–mechanistic extension of the proposed categorical approach to the diverse roles of ACs in bipolar disorders requires systematic clinical investigation of more precise relationships between psychotropic profiles and discrete mechanisms of action to assess its merits.
Abstract: Anticonvulsant drugs (ACs) have diverse antiseizure, psychotropic, and biochemical effects. Carbamazepine and valproate have mood-stabilizing actions, benzodiazepines and gabapentin have anxiolytic actions, lamotrigine is useful in rapid cycling and acute treatment and prophylaxis of bipolar depression, and topiramate and zonisamide can yield weight loss. Limited controlled data suggest the carbamazepine keto derivative oxcarbazepine has antimanic effects. A categorical approach to the diverse roles of ACs in bipolar disorders is proposed, using broad categories of ACs, on the basis of their predominant psychotropic profiles. Thus, some ACs have "sedating" profiles that may include sedation, cognitive difficulties, fatigue, weight gain, and possibly antimanic and/or anxiolytic effects. In contrast, some newer ACs have "activating" profiles that may include improved energy, weight loss, and possibly antidepressant and even anxiogenic effects. Still other newer ACs have novel "mixed" profiles, combining sedation and weight loss. A categorical-mechanistic extension of this approach is also presented, with hypotheses that "sedating" profiles might be related to prominent potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission, "activating" profiles could be related to prominent attenuation of glutamate excitatory neurotransmission, and for "mixed" profiles, sedation and weight loss might be related to concurrent GABAergic and antiglutamatergic actions, respectively. The categorical approach may have utility as an aid to clinicians in reinforcing the heterogeneity ACs, and recalling psychotropic profiles of individual ACs, but is limited as it fails to address the etiology of the heterogeneity of AC psychotropic effects. The categorical-mechanistic extension strives to address this issue, but requires systematic clinical investigation of more precise relationships between psychotropic profiles and discrete mechanisms of action to assess its merits.

52 citations


Journal ArticleDOI
TL;DR: Patients discharged from six State of Maryland inpatient mental health facilities between Jan. 1, 1997 and Dec. 31, 1997 were compared with those discharged from the two largest state facilities during the same time period on fluphenazine decanoate or haloperidoldecanoate, and the risk of readmission was lower than expected.
Abstract: Decreasing hospital admissions is important for improving outcomes for people with schizophrenia. Second-generation antipsychotics (SGAs) are better tolerated for long-term therapy than traditional medications and may contribute to a lower rehospitalization risk, but have not been compared to depot forms with regard to long-term outcomes. This study evaluates the risk of readmission in patients discharged from six State of Maryland inpatient mental health facilities between Jan. 1, 1997 and Dec. 31, 1997 on clozapine (N = 41), risperidone (N = 149), and olanzapine (N = 103). These patients were compared with those discharged from the two largest state facilities during the same time period on fluphenazine decanoate (N = 59) or haloperidol decanoate (N = 59). One-year readmission risk (measured by Kaplan-Meier survival analysis with Holm's adjustment for multiple comparison on Log Rank tests) were 10% for clozapine, 12% for risperidone, and 13% for olanzapine. These risks were not significantly lower than the readmission risk for fluphenazine decanoate (21%) but were significantly lower than haloperidol decanoate (35%) for all three SGAs. Demographic and clinical variables did not predict readmission for any of the medications. In patients with similar demographic and clinical characteristics, 1-year risk of readmission for patients treated with SGAs were at least comparable to the 1-year risk for patients receiving fluphenazine decanoate and lower than the risk for patients treated with haloperidol decanoate. SGAs may provide better long-term prognoses and outcomes for patients with schizophrenia.

51 citations


Journal ArticleDOI
Julie Birt1
TL;DR: The literature does indicate that despite fundamental cognitive and psychosocial deficits seen in patients with severe and persistent mental disorders such as schizophrenia and bipolar disorder, it is possible to effectively manage weight gain in this population.
Abstract: The prevalence of overweight and obesity in untreated patients with severe mental illness mimicks the trends seen in the general population. Furthermore, weight gain is likely to occur with the addition of pharmacotherapy with an antipsychotic. The literature does indicate that despite fundamental cognitive and psychosocial deficits seen in patients with severe and persistent mental disorders such as schizophrenia and bipolar disorder, it is possible to effectively manage weight gain in this population. In particular, behavioral interventions have been shown to be effective in the prevention and treatment of weight gain associated with antipsychotic therapy. Some success has also been seen with the use of adjunctive medication such as amantadine, histamine (H2) antagonists, metformin, topiramate, and orlistat. Additional, prospective, controlled studies of long-term antipsychotic drug associated weight gain and its clinical consequences are needed in order to identify the most effective therapy for the reduction and maintenance of body weight in patients taking antipsychotic therapy.

51 citations


Journal ArticleDOI
TL;DR: Cycles of AAS nonuse were associated with a greater percentage of subject-reported increased testicular size, appetite, frequency of sexual activity, and libido, and the results provide the first long-term, prospective evaluation of the effects of Aass, when these drugs are administered in a naturalistic pattern of abuse.
Abstract: The purpose of the study was to evaluate anabolic-androgenic steroid (AAS) abusing adults every 2 weeks with a comprehensive behavioral and clinical assessment battery. The study was conducted at the University of Pennsylvania Treatment Research Center; 10 subjects were enrolled and 7 completed the protocol. AASs and other drugs were obtained and self-administered by subjects through their usual mechanisms. On-study evaluations included medical, behavioral, and drug-use assessments. While a high incidence of mood disorders and substance abuse was found, few clinically relevant changes in physiological parameters or laboratory measures were noted throughout the study. Changes as measured by various behavioral rating scales were observed across time; however, these changes were not clearly related to periods of reported AAS use. Additional factors such as life events, subjects' other drug use, and the extended duration of activity of some of the AAS preparations probably influenced the results. Differences in subject-reported adverse effects were seen with respect to periods of AAS use and nonuse. Cycles of AAS nonuse were associated with a greater percentage of subject-reported increased testicular size, appetite, frequency of sexual activity, and libido. The results provide the first long-term, prospective evaluation of the effects of AASs, when these drugs are administered in a naturalistic pattern of abuse.

49 citations


Journal ArticleDOI
TL;DR: Olanzapine at 50 mg/day is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients and may be associated with more anticholinergic effects and weight gain than clozapine.
Abstract: Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine.

47 citations


Journal ArticleDOI
TL;DR: The newer atypical antipsychotics show promise for the treatment of PTSD, mainly ameliorating intrusive symptoms and the paucity of double-blind studies prevents firm conclusions, however, this class of medications may be useful particularly for refractory symptoms.
Abstract: To review the literature on the pharmacologic treatment of posttraumatic stress disorder (PTSD), with a focus on reports of antipsychotic use for this illness. A MEDLINE search (1966-Oct 2002) for English only articles about pharmacologic treatment of PTSD. Antipsychotic medications are being used with some frequency for PTSD. There are few studies and scant evidence to recommend the traditional antipsychotics. There are a number of reports (mostly case reports and open trials) in which atypical antipsychotics improved sleep and decreased the frequency of nightmares and flashbacks. Some studies showed global improvement across symptom clusters. The newer atypical antipsychotics show promise for the treatment of PTSD, mainly ameliorating intrusive symptoms. The paucity of double-blind studies prevents firm conclusions, however, this class of medications may be useful particularly for refractory symptoms.

43 citations


Journal ArticleDOI
TL;DR: Management of treatment-resistant depression is better served by recent attempts to create a treatment algorithm that encompasses definitive diagnosis of true TRD and strategies for optimizing available therapies, including consideration of novel treatment options.
Abstract: Managing patients with treatment-resistant depression (TRD) remains a major challenge for the practicing physician. Depression is considered treatment-resistant when at least two adequate monotherapy trials with drugs from different pharmacologic classes fail to elicit a therapeutic response. Although determining the stage of TRD may allow concise description of a patient's antidepressant history, management of TRD is better served by recent attempts to create a treatment algorithm that encompasses definitive diagnosis of true TRD and strategies for optimizing available therapies, including consideration of novel treatment options. Present strategies for managing TRD include optimization of the initial drug, substitution of another drug from the same or a different antidepressant class, combination of two antidepressants with different mechanisms of action, and adding an antidepressant drug from another class. Potential nonpharmacologic treatments include vagus nerve stimulation, repetitive transcranial magnetic stimulation, and magnetic seizure therapy as an alternative to electroconvulsive therapy. Several neuropeptides and their receptors have also been identified as potential targets for pharmacologic intervention, including corticotropin-releasing factor and substance P. Other treatments currently under investigation include augmentation of antidepressant therapy with an atypical antipsychotic agent such as olanzapine or risperidone. This kind of therapeutic intervention may prove to be especially useful in treating patients with TRD.

41 citations


Journal ArticleDOI
TL;DR: It is postulated that it is the balance between primary pathological versus secondary adaptive alterations in gene expression in the illness and their enhancement or dampening by pharmacotherapy, that may determine the episodic course of mood fluctuations and remissions.
Abstract: Many findings implicating prefrontal cortical and limbic areas of the brain and endocrine systems in the neuropathology and pathophysiology of bipolar illness have greatly increased our understanding of the neurobiology of the illness. New imaging techniques such as PET, MRI, SPECT, and MRS have detailed more evidence of specific regional alterations in the brains of bipolar patients than was thought possible just 20 years ago. These methods are beginning to be used to help predict response to treatment. Examining the mechanisms of action of mood stabilizers (such as lithium, carbamazepine, and valproate) has provided clues to potential underlying neurobiological abnormalities in the illness. Recent studies of postmortem brain tissue have begun to confirm prefrontal cortical and limbic neurochemical and microstructural alterations in patients with bipolar illness compared with controls. It is postulated that it is the balance between primary pathological versus secondary adaptive alterations in gene expression in the illness and their enhancement or dampening by pharmacotherapy, that may determine the episodic course of mood fluctuations and remissions. Further examination of the pathophysiology and neurobiology of bipolar illness should lead to both more effective treatments and, potentially, secondary and even primary episode prevention.

Journal ArticleDOI
TL;DR: The purpose of this paper is to review the scientific literature on the central nervous system effects of GBE, with emphasis on the potential mechanisms of action.
Abstract: The marketing of Ginkgo biloba extract (GBE) products is directed to the healthy, not diseased, population primarily for the promotion and maintenance of optimal brain function, not the treatment or prevention of any specific pathological state. However, recommendations are available for the use of GBE for a myriad of diseases that generally fall into one of three categories--cerebrovascular, peripheral vascular, or mitigation of tissue damage. The evidence for the pharmacological actions of GBE stem from one of three types of investigations--clinical studies in humans, pharmacological trials in animals, and in vitro studies. The purpose of this paper is to review the scientific literature on the central nervous system effects of GBE, with emphasis on the potential mechanisms of action. Limitations of the current scientific literature are highlighted and suggestions for future human and animal research directions are proposed.

Journal ArticleDOI
TL;DR: This paper reviews the existing literature regarding common side effects encountered with lithium and anticonvulsant use in patients with bipolar disorder and presents data regarding their impact on treatment adherence.
Abstract: Adverse events associated with lithium and anticonvulsant use in patients with bipolar disorder have been determined to decrease rates of treatment adherence; however, research that explores how adverse events influence treatment adherence, and which events have the greatest impact, is sparse and limited. This paper reviews the existing literature regarding common side effects encountered with lithium and anticonvulsant use in patients with bipolar disorder and presents data regarding their impact on treatment adherence. Guidelines for reducing and limiting adverse events are highlighted, as are recommendations for improving compliance associated with the experience of adverse events in the bipolar disorder population.

Journal ArticleDOI
TL;DR: Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with SSRIs, and approximately 60% of patients with MDD resistant to a prospective trial of fluoxetine experienced a full or partial response to bupropion SR.
Abstract: Up to 50% of patients with major depressive disorder (MDD) fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as an initial treatment. Switching to bupropion, for depressed patients not responding to SSRIs, is a popular strategy among clinicians. This study assesses the efficacy of bupropion SR in the management of MDD resistant to a prospective trial of fluoxetine. Twenty-nine patients with MDD refractory to an 8- to 12-week open-trial of fluoxetine were enrolled in an 8-week open-trial of bupropion SR. Both a completer analysis (n = 20) and a modified intent-to-treat analysis (n = 26) were performed to evaluate bupropion SR response rates. Using a completer analysis, seven patients (35.0%) were classified as responders, five (25.0%) partial responders, and eight (40.0%) nonresponders. A modified intent to treat analysis resulted in nine (34.6%) patients classified as responders, eight (30.8%) partial responders, and nine (34.6%) nonresponders. The overall proportion of remitters was 6/20 (30.0%) using a completer analysis and 6/26 (23.1%) using an MITT analysis. Approximately 60% of patients with MDD resistant to a prospective trial of fluoxetine experienced a full or partial response to bupropion SR. Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with SSRIs

Journal ArticleDOI
TL;DR: An analysis of predictors of medication response in bipolar disorder provides a basis for matching patients with optimal medication regimens and Randomized, controlled studies in bipolar populations are needed.
Abstract: Bipolar disorder poses many treatment challenges, including “matching” a particular patient with the optimal treatment regimen. Although there are a number of extant guidelines to assist the clinician in selecting treatment, these recommendations are largely based on general variables and fail to take into account the subtleties and complications that confront a clinician in practice. An analysis of predictors of medication response in bipolar disorder provides a basis for matching patients with optimal medication regimens. Response to treatment may depend on the polarity of an episode or on clinical features such as mixed or psychotic symptomatology and rate of cycling. Comorbid psychiatric disorders such as substance abuse, anxiety disorders, or attention-deficit/hyperactivity disorder should also be considered in designing a treatment regimen. Similarly, medical conditions, especially metabolic abnormalities or kidney insufficiency, must be taken into account. Selection of medication may also involve an analysis of demographic factors, including family and personal history of response to a particular agent. When selecting the most appropriate mood stabilizer for a patient—particularly when polypharmacy is required—the clinician should keep potential side effects and drug interactions in mind. Randomized, controlled studies in bipolar populations are needed to further characterize optimal matching of patient and medication.

Journal ArticleDOI
TL;DR: Results support the current DSM-IV definition of AD, as all AD symptoms were significantly associated with DSM- IV AD, and with most study variables.
Abstract: The definition of atypical depression (AD) has recently seen a rebirth of studies, as the evidence supporting DSM-IV atypical features criteria is weak. Study aim was to test the validity of DSM-IV definition of AD. Consecutive 202 major depressive disorder (MDD) and 281 bipolar II outpatients were interviewed, during a major depressive episode (MDE), with the Structured Clinical Interview for DSM-IV. The relationships of DSM-IV AD versus variables often reported to distinguish AD and non-AD (gender, age, onset, bipolar II, axis I comorbidity, MDE severity, residual MDE symptoms, depressive mixed state), and versus bipolar family history, were tested. Each DSM-IV AD symptom's relationship with the variables found significantly associated to DSM-IV AD was then tested, in order to assess the degree of concordance among all AD symptoms. Associations were tested by univariate logistic regression (STATA 7). Frequency of DSM-IV AD was 42.8%. DSM-IV AD was significantly more common in bipolar II versus MDD (53.7% vs. 27.7%, p = 0.0000). DSM-IV AD significant associations were the following: bipolar II, female gender, lower age, lower age of onset, residual MDE symptoms, axis I comorbidity, psychotic features, depressive mixed state, and bipolar family history. Testing associations of each DSM-IV AD symptom versus the variables found associated to DSM-IV AD showed high concordance. All AD symptoms were significantly associated with DSM-IV AD, and with most study variables. Results support the current DSM-IV definition of AD.

Journal ArticleDOI
TL;DR: The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers and the more rapid improvement with imipramine needs replication but, tentatively, it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRI.
Abstract: Despite the acknowledged favorable side effects profile of selective serotonin reuptake inhibitors (SSRIs), comparative studies have not found significant differences in efficacy between tricyclics (TCAs) such as imipramine and clomipramine, and SSRIs in the treatment of panic disorder. The present study focuses on treatment completers to inform patients who adhere to a recommended course of treatment on the possible differential patterns of improvement and of change in side effects between sertraline and imipramine. From an intent to treat consecutive sample of patients participating in the 24-week open phase protocolized treatment of a long-term controlled maintenance/discontinuation study, 20 imipramine completers and 16 sertraline completers with moderate to severe baseline symptomatology were compared using primarily repeated measures analysis of variance on measures of symptom severity, on 15 side effects systematically elicited using an inventory and on heart rate and weight. The results revealed greater early improvement with imipramine compared to sertraline but no enduring differences beyond week 8 of treatments. Side effects, in particular dry mouth, constipation, tremors, sweating, and cardiovascular complaints increased more in severity and were more frequent and persistent during imipramine than sertraline but, except for the 10 beats/min increase in heart rate, side effects were clinically insignificant at the end of both treatments. Change in sexual complaints and weight did not differ between the treatments. The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers. The more rapid improvement with imipramine needs replication but, tentatively, it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRIs.

Journal ArticleDOI
TL;DR: Current trends in the acute and long-term medication treatment of bipolar depression will be described, with particular focus on evidence from the existing literature.
Abstract: Bipolar depression is a severe, potentially lethal disorder for which there are no specific, FDA-indicated pharmacotherapies. Research in this area has been limited, and most treatments are based on unsupported extrapolation from the treatment of unipolar depression, or follow guidelines derived largely from the clinical practice experience of experts in this field. There is clearly a medical need for new and more effective treatments for bipolar depression. Recently, the newer antiepileptic drugs, and atypical antipsychotics, have been studied to evaluate their role in bridging this gap in the psychopharmacologic armamentarium. Drugs in these classes will be reviewed, in addition to serotonin reuptake inhibitors, monoamine oxidase inhibitors, and electroconvulsive therapy. In this paper, current trends in the acute and long-term medication treatment of bipolar depression will be described, with particular focus on evidence from the existing literature. Additional factors, such as side effects, risk/benefit issues, and drug-drug interactions, will be considered in an attempt to make overall recommendations for medication selection.

Journal ArticleDOI
TL;DR: This brief historical overview of bipolar disorder addresses diagnosis, treatment, cost, creativity, suicide, and stigma with a review of the literature.
Abstract: This brief historical overview of bipolar disorder addresses diagnosis, treatment, cost, creativity, suicide, and stigma with a review of the literature. This served as the introduction to the 27th Annual Scientific Meeting of the American Academy of Clinical Psychiatrists (51 references).

Journal ArticleDOI
TL;DR: A case of central pontine myelinolysis (CPM) in a patient taking lithium is reported and a rapid decrease in lithium levels might cause intracellular hyponatremia, which would be rapidly corrected because there is no actual shortage of sodium.
Abstract: Fabisiak et al. (1) report a case of central pontine myelinolysis (CPM) in a patient taking lithium. CPM was previously mentioned in this journal as a likely consequence of a rapid fall of serum lithium levels after a gradual rise to high levels (2, 3). Such rapid lithium fall is associated with neurological injury (4). The physiological background is that 1) intracellular sodium levels are about 7 meq/L, 2) lithium displaces sodium intracellular 1 and 3) CNS intracellular lithium levels are 50% above serum levels. Accordingly, a rapid decrease in lithium levels might cause intracellular hyponatremia, which would be rapidly corrected because there is no actual shortage of sodium.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the relationship between treatment-related adverse events (TRAEs) and outcome in depressed outpatients enrolled in an 8-week, 20 mg, open trial of fluoxetine.
Abstract: Treatment-related adverse events (TRAEs), particularly those that occur early on, may increase the likelihood for premature discontinuation of antidepressants. The purpose of this study was to examine the relationship between TRAEs and outcome in depressed outpatients enrolled in an 8-week, 20 mg, open trial of fluoxetine. A total of 384 patients (54.7% women, mean age 39.9 +/- 10.5 years) were enrolled in the trial. Study visits occurred at baseline and every other week. Somatic complaints were assessed during each study visit. Somatic complaints that, in the opinion of the evaluating physician, were probably related or related to treatment with fluoxetine were entered in the analysis as TRAEs. We then tested whether 1) developing at least one TRAE, 2) developing at least one moderate or severe TRAE, 3) the number of TRAEs reported during the entire trial, or 4) the number of TRAEs reported during each 2-week interval predicted whether patients would respond to fluoxetine, or prematurely discontinue treatment. None of the above scores predicted whether patients responded to or prematurely discontinued the trial. These findings failed to reveal any relationship between side effects and treatment outcome for patients with MDD enrolled in an 8-week, 20 mg, fixed dose, open trial of fluoxetine.

Journal ArticleDOI
TL;DR: Health care in America, criticized today by patients and physicians alike, developed incrementally throughout the twentieth century into a system unique to the United States.
Abstract: Health care in America, criticized today by patients and physicians alike, developed incrementally throughout the twentieth century into a system unique to the United States. Each effort to change it led to unintended consequences. There are many current proposals by presidential candidates and members of Congress for reform of the fragmentation of payment for, access to, and quality of care. There is increasing pressure from many sources to provide a solution. Will 2004 be the year we find it?

Journal ArticleDOI
TL;DR: The following remarks were transcribed from a videotape made of the memorial service held for Mandel E. Cohen, MD, on December 17, 2000, at St. John's Chapel-Episcopal Divinity School in Cambridge, Massachusetts.
Abstract: The following remarks were transcribed from a videotape made of the memorial service held for Mandel E. Cohen, MD, on December 17, 2000, at St. John's Chapel-Episcopal Divinity School in Cambridge, Massachusetts. Permission to publish these remarks was graciously given by Dr. Cohen's daughter, Anne Hamlen Cohen, MD. She was also instrumental in providing the transcripts and obtaining approval from the surviving speakers (Drs. Victor and Epps have died since the service).

Journal ArticleDOI
TL;DR: This is the last issue of the Annals that I will be responsible for editing as mentioned in this paper, and the Editor-in-Chief will be Donald W. Black, MD, Professor of Psychiatry at the University of Iowa.
Abstract: This is the last issue of the Annals that I will be responsible for editing. Beginning with the next issue, the Editor-in-Chief will be Donald W. Black, MD, Professor of Psychiatry at the University of Iowa. Sometimes we have to be told when enough is enough. In this case, I preferred not to wait until that point. My fondest desire has been that, when my time came to step down from editing the Annals, someone much better would want to carry it on. The opportunity to be followed by someone of Don Black's quality is just too good to pass up. I never dreamed that the Annals (or I as Editor) would survive for 15 years. I have complete confidence that Don will take the Annals beyond survival to the next level of success. Now I want to take advantage of my last hurrah to beat a couple of my personal drums.