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Biomedical subjects

M W Otto

Publications and source records attributed to M W Otto.

At least 73 records · Page 4Linked to original sources
PubMed1994

The relationship of alprazolam and clonazepam dose to steady-state concentration in plasma.

This report addresses the correlation between dose and concentration of both alprazolam and clonazepam in plasma. Patients were 43 participants in a double-blind, placebo-controlled study of alprazolam and clonazepam for the treatment of panic disorder. The concentration of clonazepam in plasma was linearly related with dose, measured as milligrams per day (R = 0.724; F = 24.2; p = 0.0001) or milligrams per kilogram per day (R = 0.863; F = 58.3; p = 0.0001). The correlation between drug concentration and daily dose of alprazolam was also significant (R = 0.60; F = 9.5; p = 0.007), although the correlation between dose measured as milligrams per kilogram per day and drug level was not significant (R = 0.361; F = 2.4; p = 0.14). This replicates previous findings that, for each additional milligram per day dose of alprazolam, there is a corresponding increase of approximately 10 ng/ml in the plasma and presents preliminary data that, for each added 1 mg/day dose of clonazepam, there is approximately an increase of 12 ng/ml in the plasma. For both drugs, however, there may be considerable variation in level in plasma for a given dose. Weight-adjusted clonazepam concentration may be more predictable than weight-adjusted alprazolam concentration.

Adolescent↗
PubMed1994

Cognitive behavior therapy for treatment-refractory panic disorder.

BACKGROUND: The purpose of this pilot study is to assess the efficacy of cognitive behavior therapy for the treatment of patients with panic disorder who experience an incomplete response to a trial of pharmacotherapy. METHOD: Fifteen consecutive patients with a DSM-III-R diagnosis of panic disorder referred for further treatment because of an incomplete response to pharmacotherapy were treated with 12-weeks of group cognitive behavior therapy. Patients were evaluated at baseline, endpoint, and at a mean of 2-months' follow-up to assess changes in panic attack frequency and global outcome. Eight of the 15 patients were deemed to have received an inadequate prior trial of medication at baseline, mainly because of a desire to control their symptoms without medication or fear of withdrawal and/or addiction. Seven of the patients were symptomatic at baseline despite an adequate prior trial of medication. RESULTS: Overall, patients experienced a significant improvement in global function at the end of the cognitive behavior therapy intervention, as well as a decrease in panic attack frequency. Improvement was maintained at follow-up. CONCLUSION: This study is consistent with a growing body of evidence that many patients with panic disorder remain symptomatic over time and are receiving inadequate pharmacotherapeutic treatment. Further, we observed that patients with panic disorder who are incompletely responsive or resistant to pharmacotherapeutic management may benefit from the addition of cognitive behavior therapy.

Adult↗
PubMed1994

Dysfunctional attitudes in major depression. Changes with pharmacotherapy.

High levels of dysfunctional attitudes have been associated with greater severity of depression and poorer response to pharmacological treatment. The goal of our study was to examine this relationship and the changes in dysfunctional attitudes after treatment with fluoxetine, a relatively selective serotonin uptake inhibitor. Dysfunctional attitudes were evaluated with both the Cognitions Questionnaire (CQ) and the Dysfunctional Attitudes Scale (DAS) in 115 outpatients diagnosed as having major depressive disorder. After 8 weeks of treatment with fluoxetine, 67 of these patients again completed the DAS and the CQ. Dysfunctional attitudes were associated with depression severity both before and after treatment and decreased linearly with treatment of the depression. Negative thinking and dysfunctional attitudes, as measured by both DAS and CQ, were not predictive of the degree of improvement in depressive symptoms. These findings partly support a state-dependent interpretation of dysfunctional attitudes, and provide evidence of significant reductions in these attitudes after treatment with a serotonin uptake inhibitor.

Adult↗
PubMed1993

Hemispheric activation, affective judgments, and pain perception.

This study utilized a unique contact lens method to examine the influence of right hemisphere processing on affective judgments and pain perception. Under conditions of unilateral visual stimulation, participants completed affective ratings of films and underwent a cold pressor pain task. The goal was to examine differences in affective judgments of films projected to one or the other hemisphere and to examine the influence of this unilateral visual stimulation on pain sensitivity. The results failed to replicate a previous finding of differential affective judgments under conditions of right and left visual stimulation. Nonetheless, in female subjects, unilateral visual stimulation was significantly associated with pain lateralization. This finding is discussed in terms of attentional processes in pain perception and limitations of the current lens design.

Adolescent↗
PubMed1993

Discontinuation of benzodiazepine treatment: efficacy of cognitive-behavioral therapy for patients with panic disorder.

OBJECTIVE: The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment. During treatment discontinuation, new symptoms may emerge and anxiety may return, preventing many patients from successfully discontinuing their treatment. In this controlled, randomized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines. METHOD: Outpatients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication (N = 33) were randomly assigned to one of two taper conditions: a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy. RESULTS: The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program (13 of 17; 76%) than for the patients receiving the slow taper program alone (four of 16; 25%). There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam. At the 3-month follow-up evaluation, 77% of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free. CONCLUSIONS: These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder.

Adult↗
PubMed1993

Long-term outcome after acute treatment with alprazolam or clonazepam for panic disorder.

The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder. This study examines a number of clinically relevant issues, including long-term outcome after acute treatment, the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time, evidence for dose escalation during maintenance high-potency benzodiazepine therapy, and predictors of acute and long-term response to treatment. Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase. Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies. Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia. Poor outcome at follow-up was associated with total duration of the disorder, agoraphobic subtype, and the presence of comorbid social phobia. We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment.

Adult↗
PubMed1992

Alcohol dependence in panic disorder patients.

The present study examined the prevalence of alcohol dependence among panic disorder patients. Twenty-four of 100 patients had a history of alcohol dependence according to DSM-III-R criteria; only one patient met criteria for current alcohol dependence. The lifetime prevalence obtained for this clinic sample exceeded that for the general population, and appeared to be due primarily to higher than expected rates among women. A childhood history of anxiety disorders and co-morbid diagnoses of social phobia and major depression were each associated with relatively higher rates of alcohol dependence. The clinical implications of these findings are discussed.

Adult↗
PubMed1992

The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients.

We evaluated the predictive value of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in 32 depressed outpatients completing a double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe), which failed to show any significant difference between SAMe and placebo. Treatment response was defined as the change in Hamilton Rating Scale for Depression (HRSD-24) score between baseline and the end of the six-week trial. Subjects with TSH response outside the normal range (7-25 uU/ml) had a significantly greater response than patients with a normal response. There was also a significant correlation between absolute deviations from the mean TSH response (16 uU/ml) and changes in HRSD-24 scores.

Adolescent↗
PubMed1992

A novel contact-lens system to assess visual hemispheric asymmetries.

A soft contact-lens system for achieving unilateral visual stimulation in a free vision format is described. Initial testing with light transmittance and visual perimetry indicated that the lenses created artificial visual-field deficits. The efficacy of the lenses as a technique for lateralizing visual input was evaluated by examining within-subject differences in performance on two visuospatial tasks. Speed and accuracy of performance were greater with visual input directed to the right hemisphere. These data support the lens design as a useful alternative to tachistoscopic procedures and previous lens systems.

Adult↗
PubMed1992

Cognitive-behavioral therapy for benzodiazepine discontinuation in panic disorder patients.

The discontinuation of benzodiazepine treatment in patients with panic disorder may be associated with emergent withdrawal and anxiety symptoms, relapse of panic, and the inability to complete benzodiazepine taper. Although some patients may respond to slow taper strategies or the use of pharmacologic adjuncts, many continue to experience significant difficulties during benzodiazepine discontinuation. This paper presents a cognitive-behavioral conceptualization of benzodiazepine discontinuation difficulties, emphasizing "fear of fear" cycles. From this perspective the discontinuation process is seen as exposing panic disorder patients to somatic sensations associated with panic at a time when there is both increased anxiety and concern about re-emergence or worsening of panic episodes. As a consequence, patients may re-enter a cycle of catastrophic interpretations of symptoms, increased vigilance and fear, and panic. Cognitive-behavioral interventions may ameliorate discontinuation-associated difficulties and prevent the return of the panic disorder. Preliminary data supporting the efficacy of these interventions are described.

Anti-Anxiety Agents↗
PubMed1992

Normal and abnormal information processing. A neuropsychological perspective on obsessive compulsive disorder.

This article presents a neuropsychological perspective on obsessive compulsive disorder (OCD) and describes some of the cognitive strengths and weaknesses that characterize the disorder. Neuroanatomic findings and theories of the neurologic basis of OCD are reviewed as are studies that use neuropsychological assessments. Findings of frontal lobe and/or basal ganglia dysfunction as well as memory deficits are emphasized. This information is then discussed in the context of cognitive-behavioral and information processing perspectives that emphasize normal patterns in anxiety and worry. The goal is to provide an integrated conceptual model of OCD, identifying the normal and abnormal information processing patterns that characterize the disorder.

Anxiety↗
PubMed1991

Perceptual asymmetry, plasma cortisol, and response to treatment in depressed outpatients.

Perceptual asymmetries as indicated by dichotic listening tasks have been associated with both subtype of depression and response to antidepressant treatment. To examine the association between this relatively new measure and more traditional measures of hypothalamic-pituitary-adrenal axis (HPA) activation in depression, we assessed perceptual asymmetry and basal plasma cortisol in a sample of depressed outpatients undergoing a double-blind, placebo-controlled medication trial. Each measure was examined for its ability to predict response to treatment. Perceptual asymmetry was significantly associated with plasma cortisol levels, and was also a significant predictor of treatment response. The association between plasma cortisol and treatment response did not reach significance. Our findings are limited by relatively small sample sizes but encourage further examination of perceptual asymmetry measures as predictors of treatment response and in relation to HPA activation in depression.

Adult↗
PubMed1991

Major depression in panic disorder patients with comorbid social phobia.

Rates of depression among panic disorder patients are particularly elevated in patients with comorbid social phobia. However, it is unclear whether this association is specific to social phobia, or whether any comorbid anxiety disorder increases the risk of depression. We assessed 100 panic disorder patients and found a significantly higher incidence of lifetime major depression for panic patients with comorbid social phobia or generalized anxiety disorder (GAD). Panic patients with comorbid social phobia had significantly higher scores on measures of dysfunctional attitudes and lower scores on measures of assertiveness; these variables may mediate the link between social phobia and depression in this population.

Adult↗
PubMed1991

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder.

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.

Adult↗
PubMed1990

Longitudinal course of panic disorder: findings from the Massachusetts General Hospital Naturalistic Study.

Clinical experience and controlled studies confirm the efficacy of pharmacologic and cognitive-behavioral interventions for the acute treatment of panic disorder and agoraphobia. However, while some patients experience long periods of true remission, panic disorder remains chronic for many, with intermittent periods of acute exacerbation and continued residual distress. Findings from the Massachusetts General Hospital Naturalistic Study of the Longitudinal Course of Panic Disorder suggest that (1) a number of factors contribute to the severity and persistence of panic disorder, including phobic subtype, comorbid anxiety disorders, depression, personality disorders, and anxiety sensitivity; (2) chronicity is common; (3) for some, an anxiety diathesis is manifested early in childhood and sets the tone for later chronicity and comorbidity; (4) maladaptive personality characteristics may be manifestations of an underlying anxiety disorder; (5) patients with continued symptomatology despite improvement may benefit from the flexible integration of pharmacologic and cognitive-behavioral treatment approaches; and (6) long-term treatment is indicated for many patients.

Alprazolam↗
PubMed1989

Depression, pain, and hemispheric activation.

The present study attempts to delineate the role of hemispheric activation in depression and pain. It was hypothesized that the right hemisphere is specialized to become activated by and to process negative affective stimuli, and that this specialization may play a role in the co-occurrence of depression and pain. The relationship between depression, experimental pain, and cerebral laterality was investigated in 16 depressed and 16 nondepressed, right-handed, female students. Cerebral laterality was measured via tasks assessing visual and auditory biases, and pain was assessed via a cold pressor task. The proposition that the right hemisphere mediates the co-occurrence of pain and depression was not supported, but specific findings did suggest that the right hemisphere may play a unique role in pain perception. Data from the visual task indicated that prior exposure to pain results in increased right hemisphere activation as indicated by a left visual field bias. Pain perception was a complex function of mood, preceding tasks, and the hand tested, and it was suggested that exposure to a typical right-hemisphere task increased the left side lateralization of pain in nondepressed subjects. Implications of these findings are discussed for coexisting problems of pain and depression and for the lateralization of pain in disorders judged to involve a significant psychogenic component.

Adolescent↗
PubMed1987

Right hemisphere involvement in depression: toward a neuropsychological theory of negative affective experiences.

Several lines of inquiry provide converging evidence for a critical role for the right cerebral hemisphere in negative affective experiences. This research includes the assessment of affective consequences of both focal cerebral lesions and pharmacological inactivation of one or the other hemisphere, as well as experimental and physiological techniques assessing differential hemispheric activation. The specific nature of right hemispheric involvement is conceptualized as a tendency to become activated by aversive experiences, and once activated, to process stimuli in a manner consistent with the right hemisphere's more negative affective tone. A theory of right hemisphere involvement in depressive affect is presented in detail and its relevance to clinical phenomena, e.g., the co-occurrence of depression and pain, and sex differences in depression, is examined, as is congruence with cognitive theories of depression.

Affective Symptoms↗