Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. A randomized controlled trial of fluoxetine and cognitive behavioral therapy in adolescents with major depression, behavior problems, and substance use disorders. A memory assessment technique for use in geriatric psychopharmacology: drug efficacy trial with naftidrofuryl. The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study. A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication. Prospective preliminary analysis of the development of autism and epilepsy in children with infantile spasms. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. Tayside-Fife clinical trial of cognitive-behavioural therapy for medication-resistant psychotic symptoms. Results to 3-month follow-up. The effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder.
To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression.
                Pragmatic randomised controlled superiority trial.
                6 outpatient clinics in Manchester and Cambridge.
                208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included.
                103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase.
                Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale.
                At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved.
                For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone.
                Current Controlled Trials ISRCNT 83809224. To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder, substance use disorder (SUD), and conduct disorder (CD) in adolescents receiving cognitive behavioral therapy (CBT) for SUD.
                Randomized controlled trial.
                A single-site study conducted between May 2001 and August 2004.
                One hundred twenty-six adolescents aged 13 to 19 years recruited from the community and meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria for current major depressive disorder, lifetime CD, and at least 1 nontobacco SUD.
                Sixteen weeks of fluoxetine hydrochloride, 20 mg/d, or placebo, with CBT.
                For depression, Childhood Depression Rating Scale-Revised and Clinical Global Impression Improvement; for SUD, self-reported nontobacco substance use and urine substance use screen results in the past 30 days; and for CD, self-reported symptoms in the past 30 days.
                Fluoxetine combined with CBT had greater efficacy than did placebo and CBT according to changes on the Childhood Depression Rating Scale-Revised (effect size, 0.78) but not on the Clinical Global Impression Improvement treatment response (76% and 67%, respectively; relative risk, 1.08). There was an overall decrease in self-reported substance use (4.31 days; 95% confidence interval, 2.12-6.50) and CD symptoms (relative risk, 1.20; 95% confidence interval, 0.82-1.59), but neither difference between groups was statistically significant. The proportion of substance-free weekly urine screen results was higher in the placebo-CBT group than in the fluoxetine-CBT group (mean difference, 2.10; 95% confidence interval, 0.37-4.15).
                Fluoxetine and CBT had greater efficacy than did placebo and CBT on one but not both depression measures and was not associated with greater decline in self-reported substance use or CD symptoms. The CBT may have contributed to higher-than-expected treatment response and mixed efficacy findings, despite its focus on SUD. This study was conducted to compare an automated test of paced stimulus material (Sperling's Perceptual Trace, SPT) with several other standard memory scales. Sixty patients with mild senile organic brain syndrome were divided into two groups of 30; one group was treated for 90 days with 300 mg daily of naftidrofuryl (Praxilene), and the other group received placebo. The patients were tested before treatment and at 30, 60 and 90 days after the beginning of treatment. The data indicated that the SPT indirectly assesses short-term memory, is resistant to practice effects, and is drug-sensitive. It is suggested that the SPT might become the test of choice in the indirect assessment of short-term memory in the elderly. To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined.
                The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period.
                After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age.
                Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion. To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.
                A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.
                Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).
                The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research. The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism. A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) report sexual dysfunction. SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens. This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction. Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index (primary efficacy outcome measure) and the Clinical Global Impression Scale adapted for sexual function (secondary efficacy outcome measure). End point treatment satisfaction was assessed using a Visual Analog Scale. A total of 218 women (25-45 years old) with SSRI-induced sexual dysfunction were randomized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d. (n = 109) or placebo (n = 109). The mean (SD) for Female Sexual Function Index total score was higher in the bupropion sustained release group (25.9 (5.12), 95% confidence interval (CI) 22.2-29.4) than in the placebo group (17.2 (4.9), 95% CI 15.8-20.1) (p = 0.001). Mean (SD) Clinical Global Impression Scale score for the bupropion group (2.4 (0.6), 95% CI 2.0-3.6) was significantly lower than that for the placebo group (4.2 (0.8), 95% CI 3.4-5.4) (p = 0.001). At the end of the trial the mean (SD) scores for desire (4.1 (0.7), 95% CI 3.5-4.8) (p = 0.001), arousal (4.4 (0.6), 95% CI 3.7-4.8) (p = 0.01), lubrication (4.4 (0.4), 95% CI 3.3-4.8) (p = 0.001), orgasm (4.4 (0.5), 95% CI 3.7-4.7) (p = 0.001), and satisfaction (4.2 (0.7), 95% CI 3.4-4.8) (p = 0.001) were significantly higher in the bupropion group. The highest improvement was observed in sexual desire, followed by lubrication. Compared with baseline, desire and lubrication domains increased by 86.4% (95% CI 64.9-102.2%, p = 0.001) and 69.2% (95% CI 44.7-82.6%, p = 0.001) in the bupropion group. Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction. Evidence for the efficacy of cognitive-behavioural therapy for schizophrenia is promising but evidence for clinical effectiveness is limited.
                To test the effectiveness of cognitive-behavioural therapy delivered by clinical nurse specialists in routine practice.
                Of 274 referrals, 66 were allocated randomly to 9 months of treatment as usual (TAU), cognitive-behavioural therapy plus TAU (CBT) or supportive psychotherapy plus TAU (SPT) and followed up for 3 months.
                Treatment effects were modest but the CBT condition gave significantly greater improvement in overall symptom severity than the SPT or TAU conditions combined (F (1,53)=4.14; P=0.05). Both the CBT and SPT conditions combined gave significantly greater improvement in severity of delusions than did the TAU condition (F (1,53)=4.83; P=0.03). Clinically significant improvements were achieved by 7/21 in the CBT condition (33%), 3/19 in the SPT condition (16%) and 2/17 in the TAU condition (12%).
                Cognitive-behavioural therapy delivered by clinical nurse specialists is a helpful adjunct to routine care for some people with chronic psychosis. The efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy.
                Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year.
                Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two-year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group.
                Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS.
Medication appears effective in treating SP over the short term (particularly amongst the SSRIs), and the long term. Nevertheless, the possibility of publication bias has to be acknowledged. Additional issues for future research include the use of medication in children and adolescents with SP, SP with comorbid psychiatric disorders, and performance anxiety.