Combination of inositol and serotonin reuptake inhibitors in the treatment of depression. Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. 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 effectiveness trial of collaborative care for patients with panic disorder in primary care. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Psychodynamic psychotherapy and clomipramine in the treatment of major depression. Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study. Placebo-controlled treatment trial of depression in elderly physically ill patients. Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?
Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI).
                Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks.
                No significant difference was found between the two treatment groups.
                Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol. The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study.
                Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed.
                The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups.
                Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe. 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. 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 enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice. The authors compared a combination of clomipramine and psychodynamic psychotherapy with clomipramine alone in a randomized controlled trial among patients with major depression.
                Seventy-four patients between the ages of 20 and 65 years who were assigned to ten weeks of acute outpatient treatment for major depression were studied. Bipolar disorder, psychotic symptoms, severe substance dependence, organic disorder, past intolerance to clomipramine, and mental retardation were exclusion criteria.
                Marked improvement was noted in both treatment groups. Combined treatment was associated with less treatment failure and better work adjustment at ten weeks and with better global functioning and lower hospitalization rates at discharge. A cost savings of 2,311 dollars per patient in the combined treatment group, associated with lower rates of hospitalization and fewer lost work days, exceeded the expenditures related to providing psychotherapy.
                Provision of supplemental psychodynamic psychotherapy to patients with major depression who are receiving antidepressant medication is cost-effective. 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. To determine the response of physically ill elderly depressed patients to treatment.
                Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.
                Response rate as defined by the 17-item Hamilton Depression Rating Scale.
                Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).
                The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important. Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension.
                Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months.
                No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy.
                Small sample size (N=50) limited power and rendered conclusions tentative.
                Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.
                Copright 2002 Elsevier Science BV.
TCAs, SSRIs and MAOIs are effective in the treatment of older community patients and inpatients likely to have severe physical illness. At least six weeks of antidepressant treatment is recommended to achieve optimal therapeutic effect. There is little evidence concerning the efficacy of low dose TCA treatment. Further trials are required before low dose TCA treatment is routinely recommended.