A controlled trial of treatments for generalized anxiety. Does brief dynamic psychotherapy reduce the relapse rate of panic disorder? Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Cognitive-behavioral treatment combined with asthma education for adults with asthma and coexisting panic disorder. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. Psychotherapy alone and combined with pharmacotherapy in the treatment of depression. A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone. A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care.
Treatments for chronic anxiety have received considerable interest recently. Firstly, there is a body of research which has shown problems of dependence and habituation in the long-term use of anti-anxiety drugs. A second development is that of psychological treatments for anxiety. Because of the problems involved in the use of benzodiazepines, it is important to determine whether or not psychological treatments are a reasonable alternative when treating chronic anxiety. This study was designed to test the relative effectiveness of cognitive-behavioural therapy, anxiety management training and treatment by benzodiazepines against a waiting list control. Measures were taken on both the process and outcome of treatment. The most immediate and greatest improvements in anxiety were seen in the group receiving drugs. However, these improvements reduced as the trial progressed and were minimal at the end of therapy. Both psychological treatment groups improved as the trial progressed with the most significant and consistent changes seen in the cognitive-behaviour therapy group. However, at follow-up there was no difference between the two groups receiving psychological treatments. Because of their lack of sustained improvement, over half of the group receiving drugs refused to wait without treatment until the follow-up assessment. Although panic disorder can be effectively alleviated by drug treatment, the relapse rate is high. By adding brief dynamic psychotherapy focused on the psychosocial vulnerability of patients with panic disorder to an established drug treatment regimen, we hypothesized that this would result in a lower relapse rate after pharmacotherapy.
                Patients with panic disorder (defined by DSM-III-R) were randomized to treatment with either clomipramine for 9 months (n = 20), or clomipramine for 9 months combined with 15 weekly sessions of brief dynamic psychotherapy (n = 20). Measures of anxiety and depression were collected at intake and at regular intervals. The patients had blind follow-up interviews at 6, 12, and 18 months after beginning treatment.
                All patients in both groups became free of panic attacks within 26 weeks of the start of treatment. On termination of pharmacotherapy, the relapse rate was significantly higher in the clomipramine-only group during the follow-up period. There were significantly lower scores for most anxiety measures in the clomipramine plus psychotherapy group at the 9-month follow-up.
                The addition of brief dynamic psychotherapy to treatment with clomipramine significantly reduces the relapse rate of panic disorder compared with clomipramine treatment alone. A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2x20) were included into the study. WS1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment. Panic disorder is a prevalent, often disabling condition among patients in the primary care setting. Although numerous studies have assessed the effectiveness of treatments for depression in primary care, few such studies have been conducted for panic disorder.
                To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting.
                Randomized, controlled study comparing intervention to treatment as usual.
                Six primary care clinics associated with 3 university medical schools, serving an ethnically and socioeconomically diverse patient population.
                Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder. Comorbid mental and physical disorders were permitted, provided these did not contraindicate the treatment to be provided and were not acutely life threatening.
                Patients were randomized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions (across 12 weeks) of cognitive-behavioral therapy (CBT) modified for the primary care setting, with up to 6 follow-up telephone contacts during the next 9 months, and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist. Behavioral health specialists, the majority inexperienced in CBT for panic disorder, were trained to deliver the CBT and coordinated overall care, including pharmacotherapy.
                Proportion of subjects remitted (no panic attacks in the past month, minimal anticipatory anxiety, and agoraphobia subscale score <10 on Fear Questionnaire) and responding (Anxiety Sensitivity Index score <20) and change over time in World Health Organization Disability Scale and short form 12 scores.
                The combined cognitive-behavioral and pharmacotherapeutic intervention resulted in sustained and gradually increasing improvement relative to treatment as usual, with significantly higher rates at all points of both the proportion of subjects remitted (3 months, 20% vs 12%; 12 months, 29% vs 16%) and responding (3 months, 46% vs 27%; 12 months, 63% vs 38%) and significantly greater improvements in World Health Organization Disability Scale (all points) and short form 12 mental health functioning (3 and 6 months) scores. These effects were obtained in spite of similar rates of delivery of guideline-concordant pharmacotherapy to the 2 groups.
                Delivery of evidence-based CBT and medication using the collaborative care model and a CBT-naive, midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder. This study tested the efficacy of a nurse-administered 8-week group treatment program for adults with asthma suffering from coexisting panic disorder. The program consisted of cognitive behavioral treatment (CBT) for panic disorder combined with asthma education (AE). Forty-eight women with a confirmed diagnosis of asthma and panic disorder were randomly allocated to a treatment condition (n=25) and a wait-list control condition (n=23). Twenty-five participants--15 in the treatment group and 10 in the wait-list control group--completed treatment. Repeated measures ANOVA procedures were used to compare the groups on panic and asthma outcomes at posttreatment and 6-month follow-up. The results demonstrate that the CBT-AE program is capable of producing substantial and durable antipanic and antianxiety treatment effects and led to substantial but nonsustained improvement in morning peak-flow expiratory rate and asthma-related quality of life. Implications of these findings for this clinical population are addressed. Panic disorder (PD) may be treated with drugs, psychosocial intervention, or both, but the relative and combined efficacies have not been evaluated in an unbiased fashion.
                To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo, whether one treatment is more effective than the other, and whether combined therapy is more effective than either therapy alone.
                Randomized, double-blind, placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998.
                A total of 312 patients with PD were included in the analysis.
                Patients were randomly assigned to receive imipramine, up to 300 mg/d, only (n=83); cognitive-behavioral therapy (CBT) only (n=77); placebo only (n=24); CBT plus imipramine (n=65); or CBT plus placebo (n=63). Patients were treated weekly for 3 months (acute phase); responders were then seen monthly for 6 months (maintenance phase) and then followed up for 6 months after treatment discontinuation.
                Treatment response based on the Panic Disorder Severity Scale (PDSS) and the Clinical Global Impression Scale (CGI) by treatment group.
                Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS (response rates for the intent-to-treat [ITT] analysis, 45.8%, 48.7%, and 21.7%; P=.05 and P=.03, respectively), but were not significantly different for the CGI (48. 2%, 53.9%, and 37.5%, respectively). After 6 months of maintenance, imipramine and CBT were significantly more effective than placebo for both the PDSS (response rates, 37.8%, 39.5%, and 13.0%, respectively; P=.02 for both) and the CGI (37.8%, 42.1%, and 13.0%, respectively). Among responders, imipramine produced a response of higher quality. The acute response rate for the combined treatment was 60.3% for the PDSS and 64.1% for the CGI; neither was significantly different from the other groups. The 6-month maintenance response rate for combined therapy was 57.1% for the PDSS (P=.04 vs CBT alone and P=.03 vs imipramine alone) and 56.3% for the CGI (P=.03 vs imipramine alone), but not significantly better than CBT plus placebo in either analysis. Six months after treatment discontinuation, in the ITT analysis CGI response rates were 41.0% for CBT plus placebo, 31.9% for CBT alone, 19.7% for imipramine alone, 13% for placebo, and 26.3% for CBT combined with imipramine.
                Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance. Each treatment worked well immediately following treatment and during maintenance; CBT appeared durable in follow-up. JAMA. 2000;283:2529-2536 The relative efficacy of psychotherapy and combined therapy in the treatment of depression is still a matter of debate.
                To investigate whether combined therapy has advantages over psychotherapy alone.
                A 6-month randomised clinical trial compared Short Psychodynamic Supportive Psychotherapy (n=106) with combined therapy (n=85) in ambulatory patients with mild or moderate major depressive disorder diagnosed using DSM-IV criteria. Antidepressants were prescribed according to a protocol providing four successive steps in case of intolerance or inefficacy: venlafaxine, selective serotonin reuptake inhibitor, nortriptyline and nortriptyline plus lithium. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression, the Clinical Global Impression of Severity and of Improvement, and the depression sub-scale of the Symptom Checklist.
                The advantages of combining antidepressants with psychotherapy were equivocal. Neither the treating clinicians nor the independent observers were able to ascertain them, but the patients experienced them clearly.
                The advantages of combining antidepressants with psychotherapy are equivocal. Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone.
                161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo.
                Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0.
                Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized. Effectiveness studies have tested interventions to improve quality of care for depression in primary care, but none, to our knowledge, have been completed for panic disorder (PD) in this setting. This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of "collaborative care" (CC).
                One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or "usual care" (UC). Patients in CC (n = 57) received educational videotapes and pamphlets; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks; and up to 5 telephone calls between 3 and 12 months' follow-up. Usual care patients (n = 58) were treated by their primary care physician. Telephone assessments of panic, anxiety sensitivity, depression, and disability variables were performed at 3, 6, 9, and 12 months' follow-up. Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies.
                Patients in CC were more likely to receive adequate (type, dose, duration) medication and more likely to adhere to this medication at 3 and 6 months. Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety, depression, and disability measures, with the greatest effects at 3 and 6 months.
                Compared with UC, CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients. Clinical differences were greatest in the first 6 months, corresponding to the greater quality of care and the greater intensity of intervention.
The review established the paucity of high quality evidence investigating the efficacy of psychotherapy combined with benzodiazepines for panic disorder. Currently, there is inadequate evidence to assess the clinical effects of psychotherapy combined with benzodiazepines for patients who are diagnosed with panic disorder.