Discussion: using benzodiazepines in clinical practice.
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Alcoholism↗
Biomedical subjects
Mark H Pollack
Publications and source records attributed to Mark H Pollack.
The pharmacotherapy of panic disorder.
Panic disorder is common and associated with significant morbidity and dysfunction. The pharmacologic treatment of panic disorder is aimed at reducing or eliminating panic attacks, avoidance behavior, anticipatory anxiety, and comorbid conditions--and substantially improving and normalizing overall function and quality of life. Antidepressants and benzodiazepines remain the current mainstays of pharmacotherapy for panic disorder, although other novel agents and strategies are becoming available and may add effective alternatives to the therapeutic armamentarium.
Anticonvulsants↗
Comorbid anxiety and depression.
Anxiety and depressive disorders often occur as comorbid illnesses and share many common symptoms. Risk factors for these disorders most likely include interactions of environmental and genetic factors. The presence of comorbid anxiety and depression adversely affects clinical and treatment outcomes. Selective serotonin reuptake inhibitors are usually considered first-line treatment for patients with these disorders, although alternative antidepressants or additional therapies are often necessary. Studies suggest that benzodiazepines, anticonvulsants, and atypical antipsychotics may be effective as augmentation therapy to optimize outcome, with buspirone and beta-blockers useful in some patients as well. Cognitive-behavioral therapy is also an effective therapeutic alternative for affected patients.
Anticonvulsants↗
Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment.
Cerebral bioenergetic and phospholipid abnormalities have been reported in heroin-dependent subjects. The goal of the present study was to characterize the neurochemical profile of subjects voluntarily enrolled in a methadone maintenance (MM) treatment program to overcome their heroin addiction. Participants included 43 heroin-dependent subjects during their first month of MM and 15 age-matched healthy individuals. Phosphorus magnetic resonance spectroscopy ((31)P MRS) and transverse relaxation times (T2-RT), which can reflect steady state cerebral perfusion and metabolism, were acquired at 1.5 T from an axial slice prescribed through the orbitofrontal and occipital cortices, including basal ganglia and frontal cortex. MM subjects exhibited reduced phosphocreatine (PCr) levels (-15.3%), elevated phosphodiesters (+ 12.9%, PDE) and significantly longer T2-RT ((+) 2.1%) compared with healthy comparison subjects. When MM subjects were stratified into subgroups based on treatment duration, we found a treatment duration effect on metabolite values but not T2-RT; reduced PCr was observed only after 8+ days of MM, and phosphomonoesters (PME) were elevated in the 15-28 day MM group. Taken together, these cross-sectional data suggest that the first month of MM treatment may be associated with altered cerebral bioenergetics and phospholipid metabolite levels.
Adenosine Triphosphate↗
White matter hyperintensities in subjects with cocaine and opiate dependence and healthy comparison subjects.
The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n=32) and opiate dependence (n=32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n=32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios=2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio>3.25 for deep WMH; odds ratio>4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents.
Adult↗
Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial.
RATIONALE: There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition. OBJECTIVE: To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD. METHOD: Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150-225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item (score 1 or 2), and the proportion of remitters (defined as an LSAS score of <or=30). RESULTS: Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150-225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER (at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P<0.001); corresponding remission rates were 31% and 16% (P<0.01). There were no differences in outcome according to venlafaxine ER dosage. CONCLUSIONS: Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade.
Adult↗
Moderating effects of major depression on patterns of comorbidity in patients with panic disorder.
Given the high rate of co-occurring major depression in patients with panic disorder, it is unclear whether patterns of comorbidity in individuals with panic disorder reported in the literature are associated with panic disorder or with the presence of major depression. Subjects were 231 adult subjects with panic disorder and major depression (n=102), panic disorder without comorbid major depression (n=29), major depression without comorbid panic disorder (n=39), and neither panic disorder nor major depression (n=61). Subjects were comprehensively assessed with structured diagnostic interviews that examined psychopathology across the life cycle. Panic disorder, independently of comorbidity with major depression, was significantly associated with comorbid separation anxiety disorder, simple phobia, obsessive-compulsive disorder, generalized anxiety disorder, and agoraphobia. Major depression, independently of comorbidity with panic disorder, was significantly associated with comorbidity with psychoactive substance use disorders and childhood disruptive behavior disorders. Overanxious disorder was associated with both panic disorder and major depression. Major depression has important moderating effects on patterns of comorbidity of panic disorder in referred adults.
Adult↗
Internal cue exposure and the treatment of substance use disorders: lessons from the treatment of panic disorder.
Despite early recognition of the importance of internal cues (craving sensations and emotional states) for relapse in substance use disorders, relatively little attention has been devoted to exposure-based treatments targeting these cues. Drawing upon research on the conceptualization and treatment of panic disorder, we discuss the application of internal (largely emotional) cue exposure for substance use disorders. Our model for this discussion was based on the role of exposure to feared sensations of anxiety in the treatment of panic disorder and benzodiazepine (BZ) discontinuation. Shared research strategies between panic disorder and substance use--studies of biological provocation and anxiety sensitivity--were discussed, as were gender differences in drug-use motives. In accordance with research on anxiety sensitivity, provocation effects, and the treatment of benzodiazepine withdrawal, we discussed the potential value of internal cue-exposure strategies for individuals who use substances as a way to cope with negative affect.
Anti-Anxiety Agents↗
CBT for Vietnamese refugees with treatment-resistant PTSD and panic attacks: a pilot study.
We examined the feasibility, acceptability, and therapeutic efficacy of a culturally adapted cognitive-behavior therapy (CBT) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder (PTSD) and panic attacks. These patients were treated in two separate cohorts of six with staggered onset of treatment. Repeated measures Group x Time ANOVAs and between-group comparisons indicated significant improvements, with large effect sizes (Cohen's d) for all outcome measures: Harvard Trauma Questionnaire (HTQ; d = 2.5); Anxiety Sensitivity Index (ASI: d = 4.3); Hopkins Symptom Checklist-25 (HSCL-25), anxiety subscale (d = 2.2); and Hopkins Symptom Checklist-25, depression subscale (d = 2.0) scores. Likewise, the severity of (culturally related) headache-and orthostasis-cued panic attacks improved significantly across treatment
Adult↗
Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD.
Relatively absent from previous studies of the pharmacotherapy for bipolar disorder is examination of the impact of comorbidity on treatment choices. This has occurred despite the presence of high levels of comorbid anxiety and substance use disorders, and the association of these disorders with severity and course markers of bipolar disorder. In this study, we examined comorbid disorders, identified by structured interviews, and the pharmacotherapy reported at study entry by the first 1000 patients entered into a large, multicenter study of bipolar disorder (Systematic Treatment Enhancement Program for Bipolar Disorder). Our study focused on the degree to which comorbid conditions are linked to the reported use of mood stabilizers deemed "minimally adequate" and the association between specific comorbidities and pharmacotherapy treatment, such as the use of anxiolytics in patients with anxiety disorders. Despite the presence of high levels of comorbidity, the presence of these disorders was only minimally associated with pharmacotherapy. Of the sample of bipolar outpatients, only 59% reported pharmacotherapy use meeting criteria for "minimally adequate" mood stabilizer, regardless of comorbid diagnoses, rapid cycling, or bipolar I or II status. Moreover, the cross-sectional use of "comorbidity-specific" pharmacotherapy for anxiety disorders, substance use disorders, and attention deficit disorder in this outpatient sample of patients with bipolar disorders was limited, suggesting that comorbid conditions in patients with bipolar disorder may be undertreated. Our findings highlight the need for greater clinical guidance and treatment options for patients with bipolar disorder and comorbidity.
Adult↗
Posttraumatic stress disorder in patients with bipolar disorder: a review of prevalence, correlates, and treatment strategies.
OBJECTIVES: In this article, we review the evidence for, and implications of, a high rate of comorbid posttraumatic stress disorder (PTSD) in individuals with bipolar disorder. METHODS: We reviewed studies providing comorbidity data on patients with bipolar disorder, and also examined the PTSD literature for risk factors and empirically supported treatment options for PTSD. RESULTS: Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. Risk factors for PTSD that are also characteristic of bipolar samples include the presence of multiple axis I disorders, greater trauma exposure, elevated neuroticism and lower extraversion, and lower social support and socio-economic status. CONCLUSIONS: These findings are discussed in relation to the cost of PTSD symptoms to the course of bipolar disorder. Pharmacological and cognitive-behavioral treatment options are reviewed, with discussion of modifications to current cognitive-behavioral protocols for addressing PTSD in individuals at risk for mood episodes.
Bipolar Disorder↗
Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
OBJECTIVE: The authors provide a detailed perspective on the correlates of comorbid anxiety in a large, well-characterized sample of bipolar disorder patients. METHOD: Anxiety and its correlates were examined in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS: Lifetime comorbid anxiety disorders were common, occurring in over one-half of the sample, and were associated with younger age at onset, decreased likelihood of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Although substance abuse disorders were particularly prevalent among patients with anxiety disorders, comorbid anxiety appeared to exert an independent, deleterious effect on functioning, including history of suicide attempts (odds ratio=2.45, 95% CI=1.4-4.2). CONCLUSIONS: An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated, highlighting the need for greater clinical attention to anxiety in this population, particularly for enhanced clinical monitoring of suicidality. In addition, it is important to determine whether effective treatment of anxiety symptoms can lessen bipolar disorder severity, improve response to treatment of manic or depressive symptoms, or reduce suicidality.
Adolescent↗
An open-label study of levetiracetam for the treatment of social anxiety disorder.
OBJECTIVE: Social anxiety disorder is a disabling condition characterized by excessive fear and avoidance of social and performance situations. While a variety of effective pharmacotherapies exists, many patients do not fully respond to or tolerate available agents. Preclinical and early clinical experience with levetiracetam, a novel anticonvulsant agent, suggests that levetiracetam has anxiolytic properties and a favorable adverse event profile. Levetiracetam thus warrants systematic evaluation as a treatment option for anxiety disorders. METHOD: Twenty adult outpatients who were recruited through advertisement and clinical referral and who met DSM-IV criteria for social anxiety disorder, generalized type, participated in this 8-week open-label, flexible-dose study from November 2002 to December 2003. Participants were required to have scores of >/= 50 on the Liebowitz Social Anxiety Scale (LSAS) and >/= 4 on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline. The presence of comorbid depression and anxiety disorders were permitted as long as social anxiety disorder was the primary disorder. Levetiracetam was initiated at 250 mg/day for the first week and flexibly titrated up to a maximum of 3000 mg/day (1500 mg b.i.d.). The primary outcome measure was change in the LSAS score at endpoint. RESULTS: There was a clinically significant 20.5-point decrease in LSAS scores in the intent-to-treat, last-observation-carried-forward analysis (t = 3.1; p <.01, N = 20). There were also significant reductions in CGI-S (p <.01) and Hamilton Rating Scale for Anxiety (p <.02) scores. CONCLUSIONS: This pilot study supports the safety and potential efficacy of a novel agent, levetiracetam, for the treatment of social anxiety disorder. Larger controlled trials are warranted to confirm these results.
Adult↗
Long-term management of panic disorder.
Panic disorder is a chronic, disabling condition that is often associated with a need for long-term clinical treatment. While a variety of pharmacotherapy options, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and benzodiazepines, are effective in reducing symptoms in the acute phase, a significant number of patients do not fully respond to initial treatment, and a large majority of patients experience relapse after medication discontinuation. Optimal long-term treatment of panic disorder involves attention to adequate medication dosing and adequate duration of treatment to achieve maximum improvement before discontinuing. Recent reports suggest the efficacy of adjunctive pharmacotherapies and combining pharmacotherapy with behavioral therapy to improve treatment response. Further research is necessary to determine the long-term effectiveness of these multifaceted treatment strategies among patients suffering from refractory panic disorder.
Antidepressive Agents, Tricyclic↗
Unmet needs in the treatment of anxiety disorders.
There are a number of unmet needs in the treatment of anxiety disorders including the need for more effective, rapidly acting, and better tolerated medications; early identification of nonresponse; effective treatments for refractory disorders; prevention of relapse; and promotion of resilience and long-lasting response. Rates of response to contemporary antidepressants and other anxiolytics are often less robust than might be hoped, and remission rates, which have until recently been infrequently measured, are even lower. A small number of mostly uncontrolled studies suggest a role for augmentation of initial therapy with a second modality in patients who do not fully remit to treatment. There also is a small but growing literature which suggests the use of novel anticonvulsants and atypical antipsychotics in the treatment of anxiety disorders should be further studied. However, a definitive place for these newer therapeutic strategies in the anxiety disorder treatment armamentarium awaits evidence from large, controlled studies. Psychopharmacology Bulletin. 2004;38(Suppl 1): 31-37.
Antidepressive Agents↗
Prevalence and correlates of panic attacks in postmenopausal women: results from an ancillary study to the Women's Health Initiative.
BACKGROUND: Panic attacks are known to be more common in women than in men, but the prevalence and correlates of panic in the postmenopausal period have not been well defined. METHODS: Cross-sectional survey of 3369 community-dwelling postmenopausal women enrolled between December 1, 1997, and November 30, 2000, in the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the 40-center Women's Health Initiative. Participants, aged 50 to 79 years and predominantly white (73%), completed questionnaires about the occurrence of panic attacks in the previous 6 months and about migraine headaches and underwent 24-hour ambulatory electrocardiographic monitoring. The 6-month prevalences of full-blown and limited-symptom panic attacks were calculated, and their associations with other sociodemographic and clinical variables were examined in multivariate analyses. RESULTS: One of the panic attack types was reported by 17.9% (95% confidence interval, 16.6%-19.2%) of women (full-blown attacks, 9.8%; limited-symptom attacks, 8.1%). Adjusting for age and race or ethnicity, full-blown panic attacks were more common in women with a history of migraine, emphysema, cardiovascular disease, chest pain during ambulatory electrocardiography, and symptoms of depression. Full-blown panic attacks were associated in a dose-response manner with negative life events during the past year. Panic attacks were associated with functional impairment even after adjusting for comorbid medical conditions and depression. There was no significant association with self-reported use of hormone replacement therapy. CONCLUSIONS: Panic attacks may be relatively common among postmenopausal women and seem to be associated with stressful life events, medical comorbidity, and functional impairment.
Aged↗
Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone.
Cambodian refugees with posttraumatic stress disorder (PTSD) represent a cohort in severe need of treatment, but little information is available to guide treatment choices. We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy (CBT) for treating PTSD. Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22-26 years during the Pol Pot period (1975-1979). These patients were randomly assigned to either sertraline alone or combined treatment. We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms. Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD, and that a program of CBT emphasizing information, exposure, and cognitive-restructuring can be successfully modified for Khmer-speaking refugees.
Adult↗
WCA recommendations for the long-term treatment of panic disorder.
What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12-24 months, and in some cases, indefinitely.
Adult↗