A controlled trial of treatments for generalized anxiety. A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Cognitive-behaviour therapy and medication in the treatment of obsessive-compulsive disorder: a controlled study. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. Brief antenatal cognitive behaviour therapy group intervention for the prevention of postnatal depression and anxiety: a randomised controlled trial. Cognitive and behavioral therapies alone versus in combination with fluvoxamine in the treatment of obsessive compulsive disorder.
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. 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. 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. To evaluate the effect of combining cognitive-behaviour therapy (CBT) and medication in the treatment of obsessive-compulsive disorder (OCD).
                Twenty-nine subjects diagnosed with OCD according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria were recruited through the Anxiety Clinic of Louis-H Lafontaine Hospital. They were evaluated at baseline and after treatment on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) by a psychiatrist who was blind to treatment modality. Subjects rated their degree of resistance to their rituals and the strength of their obsessional beliefs. Subjects then received 1 of 4 treatments: medication and CBT simultaneously (n = 9), CBT only (n = 6), medication while on a wait-list for CBT (n = 6), or no treatment while on a wait-list for CBT (n = 5).
                Multivariate analysis revealed that Y-BOCS scores and clinical ratings significantly improved posttreatment in all groups except the nontreatment wait-list control group. Subjects in the 2 active treatment groups receiving CBT showed reduced strength in their obsessional beliefs. The subsequent administration of CBT to those groups on the wait-list also decreased the strength of their primary obsessional beliefs and beliefs about the consequences of not performing the rituals.
                Our results suggest that either CBT or medication alone is more effective than no treatment. The combination of CBT and medication seems to potentiate treatment efficacy, and we found it more clinically beneficial to introduce CBT after a period of medication rather than to start both therapies simultaneously. This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD. Selective serotonin re-uptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) are both considered as first-line treatments for panic disorder, but the advantages of a combined therapy have yet to be definitively demonstrated. We evaluated in this pilot study the effects of combining SSRIs (vs. a placebo) with a very brief form of cognitive-behavioral therapy provided to all participants. Thirty-three subjects with DSM-IV panic disorder, with or without agoraphobia, were randomized to receive either paroxetine or a placebo with flexible dosing (10-50 mg/day). Medication visits were brief (15 min), infrequent (6 in total) and non-directive. An expert cognitive-behavior therapist administered one initial 45-min session and one subsequent 30-min session of very brief CBT (vbCBT) at weeks 5 and 7, respectively. Sessions were supplemented with educational and directive reading materials. Patients in both groups (i.e. vbCBT+paroxetine; vbCBT+placebo) improved similarly and substantially on most measures during the 10 weeks of acute treatment. At week 10, the proportion of panic-free patients was significantly higher in the paroxetine-treated group than in the placebo group (80 vs. 25%; P<0.007), as was the proportion of subjects who rated themselves as 'very much improved' at week 10 (60 vs. 13%; P<0.017). These findings point to the need for additional studies to confirm the effectiveness of very brief forms of CBT, and to document the circumstances in which combined treatment with an SSRI would be warranted. The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy.
                To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD.
                The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002.
                Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks.
                Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10.
                Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others.
                Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone. The majority of randomised controlled trials examining the effectiveness of antenatal group interventions at preventing postnatal depression in "at risk" women have used a "psychoeducational" intervention. The aim of the present study is to evaluate the effectiveness of an antenatal cognitive behavioural group intervention in a primary care setting for pregnant women identified with mild to moderate symptoms in pregnancy and/or at risk of developing depression or anxiety in the perinatal period.
                Subjects were randomised to a CBT group intervention or control condition (information booklet) and administered the EPDS and STAI at pre (Time 1) and post intervention (Time 2), and at 2 months (Time 3) and 4 months postpartum (Time 4). MINIs were administered at Times 1, 3 and 4.
                Of the 774 women approached, 277 accepted and were suitable; thus 191 were randomised to the CBT intervention and 86 to the control condition. The subsequent 52% drop-out left 89 women "completing" the CBT groups and 43 in the control group; these two groups were well matched on demographic variables. Intention to treat analyses revealed relatively low mean baseline EPDS scores (means 6.88 -8.16) with no reduction in EPDS scores in either group from Time 1 to Time 4. MINI depression criteria were fulfilled by 19% of all participants at Time 1 but there was no reduction in depression in either group; in contrast those with MINI anxiety diagnoses reduced from 28% in late pregnancy to 16% at four months postpartum in the CBT group with similar reductions in the control group. Analyses on the 132 "completers" showed significant symptomatic improvement over time for both the CBT group and control condition. Depression scores in the most symptomatic women (EPDS>12; N=19) decreased steadily by over 50% over the total time course but there were no differences in improvement between the CBT and control groups.
                A number of methodological factors may have obscured our results including a tendency to natural remission in mildly symptomatic subjects and the possibility that our control condition was therapeutic in itself.
                While a modest reduction in depression scores was noted in study "completers", both the CBT group intervention control condition were equally beneficial. The reasons for this finding include the low symptom level at baseline; the potential effectiveness of the control condition; and the brevity of the intervention. The purpose of this treatment package design study was to investigate the differential efficacy of cognitive therapy or exposure in vivo with response prevention for obsessive compulsive disorder (OCD) versus the sequential combination with fluvoxamine. Patients with OCD (N = 117) were randomized to one of the following five conditions: a) cognitive therapy for weeks 1 to 16, b) exposure in vivo with response prevention for weeks 1 to 16, c) fluvoxamine for weeks 1 to 16 plus cognitive therapy in weeks 9 to 16, d) fluvoxamine for weeks 1 to 16 plus exposure in vivo with response prevention in weeks 9 to 16, or e) waiting list control condition for weeks 1 to 8 only. Assessments took place before treatment (pretest) and after 8 (midtest), and 16 weeks (posttest). In the first 8 weeks, six treatment sessions were delivered. During weeks 9 to 16, another 10 sessions were given. Thirty-one patients dropped out. Outcome was assessed by patient-, therapist- and assessor-ratings of the Anxiety Discomfort Scale, the Yale-Brown Obsessive Compulsive Scale, and the Padua Inventory-Revised. In contrast with the four treatments, after 8 weeks the waiting list control condition did not result in a significant decrease of symptoms. After 16 weeks of treatment, all four treatment packages were effective on these OCD ratings, but they did not differ among each other in effectiveness. In OCD, the sequential combination of fluvoxamine with cognitive therapy or exposure in vivo with response prevention is not superior to either cognitive therapy or exposure in vivo alone.
Medication treatments can be effective in paediatric anxiety disorders, acting to reduce core symptoms, and should be considered as part of the treatment of these disorders. The greatest number of trials showing efficacy to date have assessed the SSRIs in treating paediatric OCD.
There is no clear evidence to show that any particular class of medication is more effective or better tolerated than any other. As quantitative data was only available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot be recommended, especially given concerns of dependency and treatment -related emergent adverse events associated with this class of drugs. 

Future RCTs could help identify potential clinical moderators of treatment efficacy. Studies of the long-term efficacy of medication treatment, optimal dosage, as well as direct comparisons of pharmacotherapy and psychotherapy are also warranted.