Effects of lockdown on emergency room admissions for psychiatric evaluation: an observational study from 4 centres in Italy.

Objectives: An observation of the Emergency Room (ER) admissions during the lockdown.Methods: We monitored admissions to the ER requiring psychiatric evaluation during the 2020 lockdown (March 9th-May 3rd, 2020) compared to the same period of 2019, in four sites of Northern Italy (ASST Lariana, AUSL Modena, ASU Friuli Centrale and AUSL Romagna). Number of admissions, baseline demographic and clinical variables were extracted from the clinical databases.Results: A 20.0% reduction of psychiatric referrals was observed across the sites (24.2% in ASST Lariana, 30.5% in AUSL Modena, 12.0% in ASU Friuli Centrale and 14.5% in AUSL Romagna). This reduction peaked at 41.5% in the first month of the lockdown. Being homeless as well as with a dual diagnosis (OR 1,67, CI: 1.02-2.74), while living in a residential facility and admission for a depressive episode Being homeless (OR 2.50, CI: 1.36-4.61) and having a dual diagnosis (OR 1,67, CI: 1.02-2.74) were significantly associated with an increase in ER admission, while living in a residential facility (OR 0.48, CI: 0.31-0.74), having a depressive episode (OR 0.36, CI: 0.18-0.73) and a diagnosis of anxiety disorder (OR 0.60, CI: 0.36-0.99) were significantly associated with a decrease.Conclusions: During lockdown, a decrease in psychiatric referrals was observed.

Adjunctive pregabalin in partial responders with major depressive disorder and residual anxiety.

BACKGROUND: Anxiety symptoms in depression result often in treatment resistance, residual symptoms, and persistent functional impairment. OBJECTIVE: To assess the effectiveness and safety of adjunctive pregabalin to antidepressants for residual anxiety in patients with major depressive disorder (MDD). METHODS: A retrospective chart review was conducted to identify partial responders among patients with MDD with residual anxiety. Twenty such patients (age, 58.4 ± 11.2 years; 15 women; baseline Hamilton Depression Rating Scale [HDRS], 17.1 ± 3.5) who received adjunctive pregabalin for residual anxiety were included. Antidepressants augmented were the selective serotonin reuptake inhibitors (n = 12), mirtazapine (n = 2), and selective serotonin-norepinephrine reuptake inhibitors (n = 6). RESULTS: Twenty patients received at least 4 weeks of pregabalin treatment after 8 weeks of antidepressant therapy. At week 1 (9 weeks after initiating treatment), pregabalin was prescribed at a mean ± SD dose of 71.2 ± 31.7 mg, and the mean maximum pregabalin dose prescribed was 156.2 ± 76.5 mg (range, 75-300 mg). At week 8, there were 13 responders (13/20 [65%]), and 7 of these 13 patients achieved remission (HDRS17 < 8). There were significant decreases in HDRS scores (13.5 ± 3.1 vs 9.1 ± 2.9, P < 0.000), and HDRS anxiety/somatization subscale scores (6.3 ± 2 to 3.6 ± 1.7, P < 0.000). Adverse effects included somnolence (n = 7), weight gain (n = 3), dizziness (n = 4), dry mouth (n = 6), edema (n = 3), blurred vision (n = 3), difficulty with concentration/attention (n = 8), headache (n = 6), and diarrhea (n = 5). CONCLUSIONS: The results suggest a possible augmentation role for pregabalin when used in conjunction with conventional antidepressants for residual anxiety in MDD.

Does the frequency of follow-up assessments affect clinical trial outcome? A meta-analysis and meta-regression of placebo-controlled randomized trials.

The number and temporal distribution of follow-up assessments during a clinical trial is a critical factor which may influence the outcome as well as the overall cost of a trial. Therefore, we aimed to examine whether the overall and differential frequency of study observations during the course of a clinical trial affects the risk ratio (RR) of responding to antidepressants vs. placebo, specifically in trials for major depressive disorder (MDD). Medline/Pubmed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD (1 January 1980-11 May 2010). A total of 142 manuscripts involving 256 drug-placebo comparison were pooled (n=38 860). We found that higher overall frequency (OF, frequency of assessments during the entire trial) and higher late frequency (LF, frequency of assessments after the first 3 wk of the trial), but not higher early frequency (EF, frequency of assessments during the first 3 wk of the trial), of follow-up visits predicted a significantly greater RR of responding to antidepressant vs. placebo (coefficient=0.213, p=0.014; coefficient=0.238, p=0.003; and coefficient=0.021, p=0.755, respectively, for OF, LF and EF). None of the measures of frequency examined (OF, EF, LF) significantly predicted the RR of discontinuing antidepressant vs. placebo. These findings suggest that increasing the number of follow-up visits, specifically after the third week rather than within the first 3 wk of the trial, may be an effective approach to improve the likelihood of success in placebo-controlled clinical trials for MDD.

Treatment of major depressive disorder and dysthymic disorder with antidepressants in patients with comorbid opiate use disorders enrolled in methadone maintenance therapy: a meta-analysis.

Depression and opiate-use disorders (abuse, dependence) often co-occur, each condition complicating the course and outcome of the other. It has been recommended that clinicians prescribe antidepressant therapy for mood symptoms in patients with active substance-use disorders, but whether antidepressants are effective in this specific population is not entirely clear. Therefore, the aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with comorbid opiate-use disorders currently in methadone maintenance treatment (MMT). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the treatment of MDD/DD in patients with comorbid opiate-use disorders currently in MMT. The search was limited to articles published between January 1, 1980, and June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in our analysis (n = 317 patients). We found no statistically significant difference in response rates between antidepressant and placebo therapy in trials of MDD/DD patients with comorbid opiate-use disorders currently in MMT (risk ratio for response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no difference in the depressive outcome of patients with comorbid opiate-use disorders on MMT whether they are on medication or placebo. Future studies examining the effectiveness of antidepressants while controlling for several variables such as psychosocial treatment and assessing the specific classes of antidepressants are needed.

The ancient Greek poet Sappho and the first case report of the fight-or-flight response.

Sappho has always been regarded as one of the greatest lyric poets of ancient Greece. Her famous poem Fragment 31 V., also known as the "Ode to Jealousy", accurately describes the profound emotional reaction triggered by the sight of her beloved. The poet's precise description of each sign and symptom triggered by this arousal makes Sappho 31 V., to the best of our knowledge, the first analytical description of the acute stress response, the so-called "fight-or-flight" response, in human history. Here, Fragment 31 V. is re-read from a medical point of view, correlating the ancient Greek lyric text, the corresponding medical terms, and the underlying catecholamine mechanism of action.

The cost of caring during recent epidemics: a rapid review of risk factors, psychological manifestations, and strategies for its treatment.

BACKGROUND: During epidemics, health care workers (HCWs) are particularly exposed to the risk of secondary trauma. If not effectively addressed, the consequences of such psychological distress can progress to more severe conditions. METHODS: A systematic search of several databases on the effect of SARS, MERS, and COVID-19 epidemics on the mental health of HCWs was performed according to both the Cochrane Handbook for Systematic Reviews of Interventions and the WHO Rapid Review Guide for Health Policy and Systems Research. RESULTS: The 77 reviewed studies highlighted that work organization and individual characteristics can add to mental health risk. Providing adequate training to prevent infection and prepare HCWs to handle the epidemic, strengthening team work to improve organization, and ensuring appropriate protective equipment is available can help prevent risk of psychiatric illness. CONCLUSIONS: Monitoring and addressing through tailored interventions the mental health consequences of pandemics in HCWs is necessary.

Early intervention service for first episode psychosis in Modena, Northern Italy: The first hundred cases.

AIM: To report on the development of an early intervention service in Modena, Italy, with information relevant to the first 4 years of implementation. METHODS: The 2-year service was offered to people aged 18-35 with psychotic manifestations, within 2 years from psychosis onset/or naïve to antipsychotics, by teams placed within community mental health Centres, according to a "specialist within generalist" model. Treatment included pharmacological consultation, psychoeducation and social inclusion programs. Health of the Nation Outcome Scale was administered at baseline and every 6 months. RESULTS: One hundred cases accepted the treatment from 1 March 2013 to 31 December 2016. Of these, 71% were male with a median age of 23. Ninety percent were diagnosed with non-affective psychosis, yielding an estimated treated incidence of 19.1/105 . General practitioners (GPs)represented the most frequent referrers to the program (38%), followed by referrals from acute general and psychiatric hospital units (22%) and self-referrals (14%). Meaningful clinical improvement was observed, 6 months after enrolment. CONCLUSIONS: An early intervention service for psychosis was successfully implemented within existing community outpatient services. GPs represented the main referrals, providing some validation of the "specialist within generalist" model of care. A promising clinical improvement and trend of reduction in duration of untreated psychosis was found, supporting the variety of early detection efforts in the community. The high median age and lack of information about pathways to care underline possible barriers to access for younger patients. These findings will inform refinement of treatments and service models for the Region.

Assessment of cardiovascular risk in an Italian psychiatric outpatient sample: A chart review of patients treated with second-generation antipsychotics.

Despite the call by the scientific community for a systematic monitoring of physical health in people with psychiatric illnesses, national and international audits have reported poor quality of cardiovascular risk assessments and management in this vulnerable population. Available evidence indicates that in people affected by mental illness, life expectancy is reduced by 10-20 years, mainly due to cardiovascular accidents and metabolic syndrome (MetS)-related diseases. The primary aim of the present study was to evaluate the accuracy of cardiovascular risk monitoring in an outpatient sample of patients taking second-generation antipsychotics. The sample consisted of 200 patients consecutively recruited from two community mental health centres. A clinical chart review was performed on the following laboratory tests: total cholesterol, high- and low-density lipoprotein, serum triglycerides, fasting blood glucose, γ-glutamyl transpeptidase. Blood pressure and waist circumference were measured. A complete cardiovascular risk assessment was available only in 60 patients out of 200 (33.3%). The only variable associated with laboratory tests for MetS was receiving three or more psychotropic medications, which increased fourfold the probability of metabolic screening. In the subsample of patients with full screening, the prevalence of MetS was 33.3%. Our findings suggest that mental health professionals working in community mental health services should incorporate a more systematic assessment of physical health in their practice, and intervene proactively to reduce the significant cardiovascular burden carried by people with several mental illness.

Correlation of articular involvement, skin disfigurement and unemployment with depressive symptoms in patients with systemic sclerosis: a hospital sample.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease associated with increased functional impairment, body image distress due to skin lesions, and psychosocial comorbidity, particularly depression. Prevalence of depressive symptoms in SSc patients ranges from 36% to 65% and it contributes to the worsening of any aspect of the disease. The aim of this study was to investigate the prevalence and clinical and non-clinical correlates of depressive symptoms in a sample of outpatients with SSc. METHODS: Seventy-eight consecutive SSc outpatients were recruited from February 2005 to July 2007. Socio-demographic and SSc-related clinical data were collected, including a modified Rodnan Skin Score, the Valentini Disease Activity Index and psycho-metric assessment of disability and pain. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Two questions on perception of support from relatives and impact of disfigurements were also directly addressed to subjects. RESULTS: The BDI mean score was 10.5 (± 8.3), with 36 subjects (46.2%) scoring above clinical significance. Unemployment, increased disability, pain, disease activity and articular involvement were significantly associated with more depressive symptoms. Older age, unemployment and more depressive symptoms were also related with complaints of disfigurements due to skin involvement. CONCLUSIONS: Depression is an influential prognostic factor in SSc. The present study contributes to the knowledge of the relationship between depression and clinical features routinely collected in rheumatology settings in order to develop a standardized assessment of psychosocial distress in routine rheumatologic procedures.

Severe and anxious depression: combining definitions of clinical sub-types to identify patients differentially responsive to selective serotonin reuptake inhibitors.

Patients with severe major depressive disorder are more likely than those with mild/moderate depression to experience the relative benefits of antidepressant therapy versus placebo. Several studies have, unexpectedly, failed to show a similar antidepressant-placebo discrepancy between patients with versus without anxious depression, although patients with anxious depression are more likely to meet criteria for severe depression than those without. The aim of this study was to confirm the absence of treatment moderating effects for anxious depression in a general clinical trial population, and to examine for the presence of treatment moderating effects in severe depression. Patient-level outcome data from all randomized, double-blind, placebo-controlled trials involving the use of the selective serotonin reuptake inhibitor escitalopram for adults with major depressive disorder sponsored by H. Lundbeck A/S or Forest Laboratories were pooled. Studies focusing on patients with a specific axis-I or -III co-morbidity were excluded. Data from five trials were pooled. Anxious depression was not found to serve as a treatment moderator for selective serotonin reuptake inhibitor therapy versus placebo. However, when patients with severe depression were analyzed separately, anxious depression significantly influenced the relative degree of symptom reduction with selective serotonin reuptake inhibitors versus placebo (p=0.0094). In fact, the numbers needed to treat for remission for these two sub-types were the largest and smallest reported to date from analyses of large datasets of antidepressants (22 for severe anxious versus 4 for severe non-anxious depression). Subdividing patients with severe major depressive disorder into those with versus without anxious depression results in the characterization of sub-types that are particularly "responsive" (severe non-anxious) and "unresponsive" (severe anxious) to selective serotonin reuptake inhibitor therapy (relative to placebo). These findings are preliminary, of yet undetermined clinical relevance, and warrant replication and further exploration.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

OBJECTIVE: The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. DATA SOURCES: PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. STUDY SELECTION: We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. RESULTS: A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that antidepressant therapy was significantly more effective than placebo in dysthymic disorder (risk ratio = 1.75; 95% CI, 1.49-2.04; P < .0001), while placebo response rates in dysthymic disorder trials were significantly lower compared to MDD trials (29.9% vs 37.9%, respectively; P = .042). Meta-regression suggested a statistically significant difference in the risk ratio of responding to antidepressants versus placebo when comparing studies either on dysthymic disorder or on MDD, suggesting a greater risk ratio for response in favor of antidepressant therapy versus placebo in patients with dysthymic disorder versus MDD (coefficient of -0.113; P = .007). CONCLUSIONS: These results support the utility of antidepressants for dysthymic disorder. In fact, the margin of efficacy of antidepressants for dysthymic disorder was larger than for MDD. Future studies providing longer-term data on the treatment of dysthymic disorder with antidepressants are essential.

Placebo-controlled, antidepressant clinical trials cannot be shortened to less than 4 weeks' duration: a pooled analysis of randomized clinical trials employing a diagnostic odds ratio-based approach.

OBJECTIVE: In double-blind, randomized, placebo-controlled clinical trials for major depressive disorder (MDD), the impact of study duration on outcome has not been adequately studied. Our aim was to examine whether placebo-controlled antidepressant trials in MDD could be shortened to less than 4 weeks. In order to accomplish this, we examined the relationship between a "positive" or "negative" finding early on (weeks 1-4), and outcome at end point. DATA SOURCES: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD published between January 1, 1980, and July 1, 2009 (inclusive). DATA SELECTION: One hundred seventy-five articles were found eligible. We obtained required measures during the required time points for 101 articles (57.7%). Final inclusion of articles was determined by consensus among the authors. DATA SYNTHESIS: One hundred eighty-two drug-placebo comparisons from 104 clinical trials were pooled (29,213 patients). The strength of the relationship between early and end point outcome increased progressively. However, only at week 4 did the diagnostic odds ratio (27.44) indicate strong concordance between early and end point outcome. The specificity of early outcome as a predictor of end point outcome did not vary substantially from visit to visit (0.91-0.92), while the sensitivity increased proportionally with each visit (from 0.17 to 0.72). CONCLUSIONS: The present analysis suggests that antidepressant clinical trials cannot be shortened to less than 4 weeks' duration, primarily due to the increased risk of erroneously concluding that an effective treatment is ineffective. Four weeks is the minimum adequate length of a trial in order to reliably detect drug versus placebo differences.

Antidepressants for major depressive disorder in patients with a co-morbid axis-III disorder: a meta-analysis of patient characteristics and placebo response rates in randomized controlled trials.

The objective of this study is to assess whether the antidepressants are effective in treating major depressive disorder (MDD) in patients with a co-morbid axis-III disorder, and to compare the relative efficacy (vs. placebo) of antidepressants between these patients and those enrolled in general MDD trials. Medline/Pubmed publication databases were searched. We selected for randomized, double-blind, placebo-controlled trials of antidepressants for MDD, whether conducted in a general population, or in populations with an axis-III disorder. Antidepressants were more effective than placebo in patients with axis-III disorders overall [risk ratio for response (RR)=1.42, P<0.0001], as well as specifically for post-stroke (RR=1.43, P=0.04), human-immunodeficiency virus positive or acquired immunodeficiency syndrome (RR=1.66, P=0.005), but not cancer patients (RR=1.26, P=0.19). There was a trend for higher placebo response rates in studies, which did (41.2%) versus those which did not (37.7%) select for axis-III disorders (P=0.06), and significantly higher antidepressant response rates in studies which did (57.4%) versus those which did not (53.5%) select for axis-III disorders (P=0.01). Antidepressants are effective for MDD in patients who present with co-morbid axis-III disorders and as effective (vs. placebo) in this population as they are in the general MDD population. Higher general response rates observed in the co-morbid MDD population are intriguing, and require replication.

Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials.

OBJECTIVE: Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders. DATA SOURCES: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder. STUDY SELECTION: 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive). RESULTS: We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or whether they were used in pure MDD or in combined MDD and dysthymic disorder populations. CONCLUSIONS: These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed.

Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.

OBJECTIVE: Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients. DATA SOURCES: PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search. STUDY SELECTION: Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials). RESULTS: Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients. CONCLUSIONS: The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear.

Relationship between probability of receiving placebo and probability of prematurely discontinuing treatment in double-blind, randomized clinical trials for MDD: a meta-analysis.

An increased likelihood of receiving placebo in randomized clinical trials has been found to predict greater chances of trial success. However, patients who are less likely to receive active therapy (and more likely to receive placebo) may be at increased risk of attrition which, in turn, can limit the statistical power of a study. Therefore, in the present work, we sought to investigate the relationship between the probability of receiving placebo and the likelihood of prematurely discontinuing treatment. Medline/Pubmed publication databases were searched for RCT in MDD. A meta-regression established that the likelihood of receiving placebo did not predict either antidepressant discontinuation rates, placebo-discontinuation rates or the risk ratio of discontinuing antidepressants versus placebo. An increased likelihood of receiving placebo did not inflate discontinuation rates which did not influence the degree of antidepressant-placebo "separation".

Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants.

OBJECTIVE: To compare patient characteristics, placebo-response rates, and outcome differences in active treatment compared to placebo in randomized controlled trials (RCTs) of complementary and alternative medicine (CAM) and standard antidepressants for major depressive disorder (MDD). DATA SOURCES: Eligible studies were first identified using searches of PubMed/MEDLINE, restricted to English, by cross-referencing the search term placebo with each of the antidepressants (those that had received letters of approval by the US, Canadian, or EU drug regulatory agencies for the treatment of MDD) and selected CAM agents. These searches were limited to articles published between January 1, 1980, and September 15, 2009 (inclusive). Reference lists from identified studies were also searched for studies eligible for inclusion. STUDY SELECTION: We selected RCTs for MDD that included validated diagnostic assessment and baseline/outcome measures of illness severity. Assessment was limited to widely used CAM agents most frequently studied in RCTs with pill placebo: St John's wort, omega-3 fatty acids, and S-adenosyl-L-methionine (SAMe). DATA SYNTHESIS: Of eligible publications, 173 reported results of 1 trial, and 5 included > 1 trial, representing a total of 185 RCTs. Patient variables, including illness severity, were similar across CAM and antidepressant RCTs, except for a higher proportion of women in CAM studies (P = .0003). Random-effects meta-analysis indicated that both antidepressant and CAM monotherapy resulted in superior response rates compared with placebo. Placebo-response rates were significantly lower for patients enrolled in CAM versus antidepressant RCTs (P = .002). Meta-regression analyses yielded no significant differences in the relative risk of prematurely discontinuing therapy due to any reason between active treatment and placebo for antidepressant and CAM RCTs, although discontinuation due to adverse events was higher in antidepressant RCTs compared to CAM RCTs (P = .007). CONCLUSIONS: Participants in CAM trials were more likely to be female and to have a lower placebo-response rate compared to those in standard antidepressant trials for MDD. Trials of standard antidepressants and CAM therapies were composed of patients with similar depression severity.