Buspirone augmentation of antidepressant therapy

Thirty outpatients meeting DSM-III-R or DSM-IV criteria for major depression, single or recurrent episode, and failing to respond to an adequate trial of an antidepressant (>6 weeks at recommended dosage) received buspirone (20-30 mg/day) for 4 or 5 weeks in addition to their existing antidepressant. Of the 22 patients who had buspirone added to their selective serotonin reuptake inhibitor antidepressant regimen (fluoxetine, paroxetine, or citalopram), 59% (13/22) showed complete or partial remission of their depressive symptomatology. Similarly, 63% (5/8) of patients treated with buspirone in addition to clomipramine showed complete or partial remission. The mean score on the Clinical Global Impressions Scale fell by 64% (from 4.7 to 1.7; p < 0.0001) in treatment responders (complete and partial). No serious side effects were observed during combination therapy. Seventy-nine percent (11/14) of initial responders (both complete and partial) who remained on augmentation therapy for at least 4 months were symptom-free at follow-up. Buspirone augmentation may produce marked clinical improvement in depressed patients who are initially unresponsive to standard antidepressant therapy.     

A risk-benefit assessment of pharmacotherapies for clinical depression in children and adolescents

Child and adolescent major depressive disorders are common and recurrent disorders. The prevalence of major depressive disorders is estimated to be approximately 2% in children and 4 to 8% in adolescents. Major depressive disorders in children are frequently accompanied by other psychiatric disorders, poor psychosocial outcome and a high risk of suicide and substance abuse, indicating the need for effective treatment and prevention. The use of antidepressant medications as the first line of treatment for children and adolescents with mild to moderate major depressive disorders has been questioned. However, some subgroups of patients may benefit from initial treatment with antidepressants. These subgroups may include patients who are unwilling or unable to undergo psychotherapy, have not responded to at least 8 to 12 sessions of psychotherapy, have bipolar, atypical or severe depression or have recurrent depression. Currently, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors are the first medication choice because of their efficacy, benign adverse effect profile, ease of use and low risk of death following an overdose. Further research in continuation and maintenance treatments, treatment of comorbid conditions, subtypes of depression, e.g. bipolar, atypical, seasonal, and combinations of pharmacotherapy and psychotherapy are needed. In addition, studies of the pharmacokinetics, pharmacodynamics and long term adverse effects of antidepressant medications in children and adolescents are warranted.     

Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression.

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paroxetine. A review of its pharmacology, therapeutic use in depression and therapeutic potential in diabetic neuropathy

Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or = 60 years) with major depression, short term (6 weeks) treatment with paroxetine produces clinical improvements significantly superior to those seen with placebo and similar to those with tricyclic antidepressant agents, mianserin and fluoxetine. There is evidence that paroxetine has positive effects on co-existing anxiety and does not precipitate agitation. Paroxetine has also shown potential in the symptomatic treatment of diabetic neuropathy; however, further clinical experience is needed to confirm this preliminary result. Short term paroxetine therapy is associated with fewer anticholinergic and CNS adverse effects, but generally more gastrointestinal disturbances, than tricyclic antidepressants and mianserin. Unlike the tricyclic agents, paroxetine does not significantly affect cardiovascular function or impair psychomotor performance. This tolerability profile should be particularly beneficial in elderly patients, who are generally more susceptible than younger patients to the anticholinergic and CNS adverse events associated with tricyclic antidepressant drugs, and in whom there is a higher prevalence of pre-existing cardiovascular disease. It also suggests an important potential advantage over tricyclic antidepressants in the setting of overdosage. Thus, primarily because of its better tolerability profile and potentially lower toxicity in overdosage and in patients with cardiovascular disease, paroxetine appears to be a more attractive option than tricyclic antidepressants for the treatment of depression in late life. Future research should attempt to define more fully the efficacy of paroxetine as long term prophylactic therapy for recurrent depression and to assess how its overall therapeutic profile compares with other selective serotonin reuptake inhibitors in the elderly.     

Prevalence and correlates of depressive syndromes among adults visiting an Indian Health Service primary care clinic

Depression is common among patients visiting primary care clinics. In order to describe the prevalence of depressive syndromes in an American Indian primary care clinic population and to help define the clinical correlates of depressive syndromes in this setting, a clinic-based research study of depression was undertaken by the Indian Health Service (IHS). One hundred and six patients from an IHS primary care clinic were systematically enlisted for participation in the study. Participants completed the Inventory for Diagnosing Depression (IDD). Twenty-two (20.7%) responded with answers scoring positive for a depressive syndrome. Nine of these 22 (8.9% of the 106 participants) met IDD criteria for a major depressive syndrome. A diagnosis of depression, a past history of depression, use of mental health facilities, unexplained pains, and antidepressant medication use were associated with the presence of a depressive syndrome.     

Prevalence and predictors of posttraumatic stress in women undergoing an ovarian cancer investigation.

This study assessed posttraumatic stress disorder (PTSD) in women being investigated for an ovarian cancer diagnosis to determine prevalence and factors predicting PTSD in these patients. Participants (N = 75) were recruited from the Princess Margaret Hospital in Toronto, Ontario, after their initial clinic appointment and given a prediagnostic assessment that included measures of PTSD, depression, stress and pain. One month later, patients received an identical postdiagnostic assessment. No cases of clinical PTSD were detected, although 13.6% of participants were identified with subsyndromal PTSD. Multiple regression analyses showed that those participants reporting significant baseline depressive symptoms, definitively diagnosed with ovarian cancer, and with shorter treatment wait times were more likely to have a significant increase in PTSD symptoms. Supportive interventions aimed at reducing PTSD symptoms, launched prior to an ovarian cancer diagnosis, might optimally be directed at patients with baseline depressive symptoms and those with shorter treatment wait times. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment response of depressed outpatients unresponsive to both a tricyclic and a monoamine oxidase inhibitor antidepressant

BACKGROUND: Data regarding effective treatment options for the minority of patients refractory to initial antidepressant trials are essential to guide therapeutic choices and to sustain the hope of patients and perseverance of clinicians. Few such data are available concerning the treatment of patients refractory to treatment with both a tricyclic antidepressant and a monoamine oxidase inhibitor given singly. METHOD: In a study of mood reactive depressed patients, most of whom met Columbia criteria for atypical depression, 20 patients refractory to vigorous 6-week double-blind trials of both imipramine and phenelzine given singly were given clinician's choice open treatment. A chart review of course in open treatment was conducted. RESULTS: Eleven patients (55%) had a full response to subsequent treatments, principally continued phenelzine and the combination of phenelzine with amitriptyline. Another 6 (30%) had at least moderate benefit from a variety of other treatments. CONCLUSION: These data suggest that even among patients who have failed to respond to two vigorous trials of different antidepressants, at least half appear to benefit from other pharmacologic regimens.     

Treatment of active-duty military with PTSD in primary care: Early findings.

The study presents early findings from an ongoing pilot study of a cognitive–behavioral treatment for assisting active-duty military members with deployment-related posttraumatic stress disorder (PTSD) designed for use by psychologists working in an integrated primary care clinic. Treatment protocol is based primarily on Prolonged Exposure but also includes elements of Cognitive Processing Therapy that were adapted for use in primary care. Individuals were recruited from the population of patients consulted to the psychologist by primary care providers during routine clinical care. The 15 participants include active-duty or activated reserve Operation Iraqi Freedom and Operation Enduring Freedom veterans seeking help for deployment-related PTSD symptoms, with a PTSD Checklist-Military Version score 32, and interest in treatment for PTSD in primary care. Baseline and 1-month posttreatment follow-up evaluations were conducted by an independent evaluator. Five participants (33%) dropped out of the intervention after one or two appointments. Using the last observation carried forward for intent-to-treat analyses, the results showed that PTSD severity, depression, and global mental health functioning all significantly improved with the intervention. Fifty percent of treatment completers no longer met criteria for PTSD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Controlled study of treatment of PTSD using EMDR in an HMO setting.

67 individuals (aged 18–73 yrs) diagnosed with posttraumatic stress disorder (PTSD) were randomly assigned to either Eye Movement Desensitization and Reprocessing (EMDR) treatment or Standard Care (SC) treatment. Participants were assessed pretreatment, after 3 sessions, and at the completion of treatment using the SCL-90, Beck Depression Inventory, Impact of Event Scale (M. Horowitz et al, 1979), modified PTSD Symptom Scale (S. A. Falsetti et al, 1993), State Trait Anxiety Inventory, and other measures. In addition, an independent evaluator assessed participants using Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) criteria for PTSD including Global Assessment of Functioning at the 3 data points. Ss in the EMDR treatment group showed significantly greater improvement with greater rapidity than those in the SC treatment group on measures of PTSD, depression, anxiety, and general symptoms. Ss who received EMDR treatment used fewer medication appointments for their psychological symptoms and needed fewer psychotherapy appointments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment of refractory depression with high-dose thyroxine

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.     

Relationship of posttreatment decentering and cognitive reactivity to relapse in major depression.

Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response was associated with gains in decentering-the ability to observe one's thoughts and feelings as temporary, objective events in the mind-and whether these gains moderated the relationship between mood-linked cognitive reactivity and relapse of major depression. Findings revealed that CBT responders exhibited significantly greater gains in decentering compared with ADM responders. In addition, high post acute treatment levels of decentering and low cognitive reactivity were associated with the lowest rates of relapse in the 18-month follow-up period. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.     

Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response

It has been reported that the 5-HT1A autoreceptor antagonist pindolol can accelerate the antidepressant response to the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine, presumably by preventing the initial decrease in firing activity of 5-HT neurons produced by the SSRI. The present study was aimed at further exploring this treatment strategy in three groups of 10 patients with unipolar major depression allocated sequentially to three treatment arms for 28 days. The administration of the selective 5-HT1A agonist buspirone (20 mg/day for 1 week and 30 mg/day thereafter) with pindolol (2.5 mg TID) was used to activate selectively postsynaptic 5-HT1A receptors. This combination produced a greater than 50% reduction of depressive symptoms in the first week in 8 of 10 patients and the response was sustained for the remainder of the trial. In contrast, the combination of tricyclic antidepressant drugs devoid of effect on the 5-HT reuptake process (desipramine or trimipramine, 75 mg/day for 1 week and 150 mg/day thereafter) with pindolol resulted in only one of ten patients achieving a 50% improvement after 28 days. The combination of the SSRI fluvoxamine (50 mg/day for 1 week and 100 mg/day thereafter) with pindolol produced a marked antidepressant effect but did not act as rapidly as the buspirone plus pindolol combination with none, four, and eight patients achieving a 50% amelioration after 7, 14, and 21 days of treatment, respectively. These results provide further evidence that pindolol may accelerate the antidepressant effect of drugs that alter the function of the 5-HT neurons and that the selective activation of postsynaptic 5-HT1A receptors may induce a rapid and robust antidepressant response.     

One-year outcomes of a randomized clinical trial treating depression in low-income minority women.

This study examines 1-year depressive symptom and functional outcomes of 267 predominantly lowincome, young minority women randomly assigned to antidepressant medication, group or individual cognitive- behavioral therapy (CBT), or community referral. Seventy-six percent assigned to medications received 9 or more weeks of guideline-concordant doses of medications; 36% assigned to psychotherapy received 6 or more CBT sessions. Intent-to-treat, repeated measures analyses revealed that medication (p = .001) and CBT (p = .02) were superior to community referral in lowering depressive symptoms across 1-year follow-up. At Month 12, 50.9% assigned to antidepressants, 56.9% assigned to CBT, and 37.1% assigned to community referral were no longer clinically depressed. These findings suggest that both antidepressant medications and CBT result in clinically significant decreases in depression for low-income minority women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comorbidity and course of psychiatric disorders in a community sample of former prisoners of war

OBJECTIVE: The authors assessed DSM-III-R disorders among American former prisoners of war. Comorbidity, time of onset, and the relationship of trauma severity to complicated versus uncomplicated posttraumatic stress disorder (PTSD) were examined. METHOD: A community sample (N=262) of men exposed to combat and imprisonment was assessed by clinicians using the Structured Clinical Interview for DSM-III-R. RESULTS: The rates of comorbidity among the men with PTSD were lower than rates from community samples assessed by lay interviewers. Over one-third of the cases of lifetime PTSD were uncomplicated by another axis I disorder; over one-half of the cases of current PTSD were uncomplicated. PTSD almost always emerged soon after exposure to trauma. Lifetime PTSD was associated with increased risk of lifetime panic disorder, major depression, alcohol abuse/dependence, and social phobia. Current PTSD was associated with increased risk of current panic disorder, dysthymia, social phobia, major depression, and generalized anxiety disorder. Relative to PTSD, the onset of the comorbid disorders was as follows: major depression, predominantly secondary; alcohol abuse/dependence and agoraphobia, predominantly concurrent (same year); social phobia, equal proportions primary and concurrent; and panic disorder, equal proportions concurrent and secondary. Trauma exposure was comparable in the subjects with complicated and uncomplicated PTSD. CONCLUSIONS: The types of comorbid diagnoses and their patterns of onset were comparable to the diagnoses and patterns observed in other community samples. The findings support the validity of the PTSD construct; PTSD can be distinguished from comorbid disorders. Uncomplicated PTSD may be more common than previous studies suggest, particularly in clinician-assessed subjects exposed to severe trauma.     

Randomized trial of prolonged exposure for posttraumatic stress disorder with and without cognitive restructuring: Outcome at academic and community clinics.

Female assault survivors (N = 171) with chronic posttraumatic stress disorder (PTSD) were randomly assigned to prolonged exposure (PE) alone, PE plus cognitive restructuring (PE/CR), or wait-list (WL). Treatment, which consisted of 9-12 sessions, was conducted at an academic treatment center or at a community clinic for rape survivors. Evaluations were conducted before and after therapy and at 3-, 6-, and 12-month follow-ups. Both treatments reduced PTSD and depression in intent-to-treat and completer samples compared with the WL condition; social functioning improved in the completer sample. The addition of CR did not enhance treatment outcome. No site differences were found: Treatment in the hands of counselors with minimal cognitive- behavioral therapy (CBT) experience was as efficacious as that of CBT experts. Treatment gains were maintained at follow-up, although a minority of patients received additional treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)