Revisiting stimulant use for emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD).

INTRODUCTION: Emotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an increasing number of studies investigated the effects of stimulant medications on ED in patients with ADHD. AREAS COVERED: A narrative review of the literature on stimulant treatment for ED is provided, including controlled and observational clinical studies conducted on pediatric and adult samples and neurobiological investigations. Positive effects of stimulants on irritability have been demonstrated in children. Comorbidity with disruptive behavior disorders (DBD) and disruptive mood dysregulation disorder does not prevent stimulant effectiveness. Methylphenidate has also been found to reduce temper problems, affective instability, and emotional over-reactivity in adults with ADHD, although with variable effect sizes. A variety of adverse emotional effects have been reported, especially at high doses and in special populations. However, several possible confounders of treatment-emergent ED have been highlighted. Finally, according to neuroimaging studies, stimulants may mitigate emotional processing anomalies associated with ADHD. EXPERT OPINION: The findings are consistent with models including ED within the core features of ADHD. Stimulant treatment should be prioritized over antipsychotics in ADHD-DBD. It remains to be elucidated whether other medications may be more effective in specific populations with ADHD and/or ED.

The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder.

Bipolar disorder (BD) is a chronic mental disorder characterized by recurrent episodes of mania and depression alternating with periods of euthymia. Although environmental and genetic factors have been described, their pathogenesis is not fully understood. Much evidence suggests a role for inflammatory mediators and immune dysregulation in the development of BD. The first-line treatment in BD are mood-stabilizing agents, one of which is lithium (Li) salts. The Li mechanism of action is not fully understood, but it has been proposed that its robust immunomodulatory properties might be one of the mechanisms responsible for its effectiveness. In this article, the authors present the current knowledge about immune system changes accompanying BD, as well as the immunomodulatory effect of lithium. The results of studies describing connections between immune system changes and lithium effectiveness are often incoherent. Further research is needed to understand the connection between immune system modulation and the therapeutic action of lithium in BD.

Eating disorders and emotional dysregulation are associated with insufficient weight loss after bariatric surgery: a 1-year observational follow-up study.

PURPOSE: Subjects with obesity, especially those seeking bariatric surgery, exhibit high rates of mental disorders and marked psychopathological traits. The primary objective of this prospective, non-interventional study was to investigate whether the presence of different psychiatric disorders, attention deficit/hyperactivity disorder (ADHD) symptomatology and emotional dysregulation influenced weight loss at 1-year follow-up after surgery. METHODS: Subjects consecutively referred for pre-surgical evaluation at the Obesity Center of Pisa University Hospital were recruited. Psychiatric diagnoses were made through the Mini-International Neuropsychiatric Interview (MINI) and ADHD symptomatology was assessed with the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Emotional dysregulation was investigated through the WRAADDS and self-report questionnaires. After surgery, weight and obesity-related comorbidities were monitored during follow-up. RESULTS: Of the 99 participants recruited, 76 underwent surgery and 65 could be reevaluated 1 year after surgery. Subjects with insufficient weight loss (excess body mass index loss ≤ 53%, n = 15) had more frequent lifetime binge eating disorder (BED) and BED-mood disorders comorbidity than subjects with favorable post-surgical outcome. Additionally, they scored higher on both physician-administered and self-report scales assessing emotional dysregulation, which represents a nuclear symptom of ADHD in adults. At the logistic regression analysis, older age, higher preoperative excess body mass index and greater affective instability were predictors of reduced weight loss at 1-year follow-up. CONCLUSION: Emotional dysregulation seems to be associated with a worse outcome after bariatric surgery. Further studies with larger samples and longer follow-up are needed to confirm the influence of different psychiatric disorders and psychopathological traits on post-surgical outcome. LEVEL OF EVIDENCE: V, prospective descriptive study.

Challenges of Treating ADHD with Comorbid Substance Use Disorder: Considerations for the Clinician.

Adults with attention deficit/hyperactivity disorder (ADHD) often present psychiatric comorbidities and, in particular, substance use disorder (SUD). ADHD-SUD comorbidity is characterized by greater severity of both disorders, earlier age of onset, higher likelihood of polydrug-abuse and suicidal behaviors, more hospitalizations, and lower treatment adherence. At the present stage, research focused on the pharmacological management of ADHD with comorbid SUD in both adolescents and adults is still lacking. Furthermore, while the short-term effects of stimulants are well studied, less is known about the chronic effects of these drugs on dopamine signaling. Current available evidence is consistent in reporting that high doses of stimulant medications in ADHD-SUD subjects have a mild to moderate efficacy on ADHD symptoms. Some data suggest that pharmacological treatment with stimulants may be beneficial for both ADHD symptoms and comorbid cocaine or amphetamine use. However, in the long run, stimulant medications may have a potential risk for misuse. For the absence of potential misuse, atomoxetine is often recommended for ADHD with comorbid cocaine or amphetamine use disorder. However, its efficacy in reducing addictive behavior is not demonstrated. In subjects with other subtypes of SUD, both atomoxetine and stimulant drugs seem to have scarce impact on addictive behavior, despite the improvement in ADHD symptomatology. In this population, ADHD treatment should be combined with SUD-specific strategies.

The role of NMDA receptors in bipolar disorder: A systematic review.

OBJECTIVES: Glutamatergic transmission and N-methyl-D-aspartate receptors (NMDARs) have been implicated in the pathophysiology schizophrenic spectrum and major depressive disorders. Less is known about the role of NMDARs in bipolar disorder (BD). The present systematic review aimed to investigate the role of NMDARs in BD, along with its possible neurobiological and clinical implications. METHODS: We performed a computerized literature research on PubMed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, using the following string: (("Bipolar Disorder"[Mesh]) OR (manic-depressive disorder[Mesh]) OR ("BD") OR ("MDD")) AND ((NMDA [Mesh]) OR (N-methyl-D-aspartate) OR (NMDAR[Mesh]) OR (N-methyl-D-aspartate receptor)). RESULTS: Genetic studies yield conflicting results, and the most studied candidate for an association with BD is the GRIN2B gene. Postmortem expression studies (in situ hybridization and autoradiographic and immunological studies) are also contradictory but suggest a reduced activity of NMDARs in the prefrontal, superior temporal cortex, anterior cingulate cortex, and hippocampus. CONCLUSIONS: Glutamatergic transmission and NMDARs do not appear to be primarily involved in the pathophysiology of BD, but they might be linked to the severity and chronicity of the disorder. Disease progression could be associated with a long phase of enhanced glutamatergic transmission, with ensuing excitotoxicity and neuronal damage, resulting into a reduced density of functional NMDARs.

A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs.

The present systematic review was aimed at critically summarizing the evidence about treatment-emergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th, 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5-16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated.

Occurrence of involuntary movements after prolonged misuse of zolpidem: a case report.

Zolpidem is a non-benzodiazepine agent used for short-term treatment of insomnia. Several cases of dependence and withdrawal from zolpidem are reported in the literature. Furthermore, involuntary movements after prolonged zolpidem misuse have been described. In this case report, a 69-year-old Italian woman with no history of diagnosed psychiatric or neurologic diseases developed uncontrolled movements and a depressive-anxious syndrome after twelve-year zolpidem misuse. The underlying mechanisms of involuntary movements occurring after long-term zolpidem intake are unknown; yet, we suggest that zolpidem might induce an increase in dopamine release through inhibition of gamma-aminobutyric acid neurons tonically suppressing dopamine cells. Future studies on the occurrence of persistent disorders after long-term benzodiazepine or Z-drug abuse are needed and clinicians should pay attention to the risk of tardive syndromes related to zolpidem misuse, especially in the case of long-term intake of over-therapeutic dosages.

Pharmacotherapy for bipolar disorder in adults with high-functioning autism.

INTRODUCTION: The association between high-functioning autism (HFA) and bipolar disorder (BD) in adult subjects has been confirmed by a growing number of studies. However, identifying and treating BD in this population is a clinical challenge and requires careful assessment and adequate knowledge of both disorders. AREAS COVERED: This review aims to provide a clinical presentation of mood episodes in HFA individuals, and an update on the pharmacotherapy of BD in these individuals, sharing with the reader expert opinion on the current state of the art and future perspectives. EXPERT OPINION: BD has an atypical clinical presentation in HFA subjects with the possibility of diagnostic and therapeutic mistakes. Despite the absence of controlled studies, the available evidence indicates mood stabilizers, especially lithium, as the first treatment option. HFA subjects are particularly vulnerable to pharmacological side effects, such as extrapyramidal and catatonic symptoms with antipsychotics, or activation syndrome with antidepressants. Accordingly, initial titration of these drugs should be slow and their use should be limited in time. Among antipsychotics, dopamine receptor antagonists with combined serotonergic activity are preferable. Further research is needed to improve the diagnostic process and to delineate the effectiveness of different drugs for BD in HFA subjects.

BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression.

Background: Major depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge. Methods: A total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained. Results: After the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77). Conclusion: Results suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.

Prevalence of mood, panic and eating disorders in obese patients referred to bariatric surgery: patterns of comorbidity and relationship with body mass index.

PURPOSE: We aimed at investigating the lifetime prevalence of mood, eating and panic disorders in a large sample of obese patients referred to bariatric surgery. We also explored the patterns of psychiatric comorbidity and their relationship with Body Mass Index (BMI). METHODS: The sample was composed of patients consecutively referred for pre-surgical evaluation to the Obesity Center of Pisa University Hospital between January 2004 and November 2016. Clinical charts were retrieved and examined to obtain sociodemographic information, anthropometric variables and lifetime psychiatric diagnoses according to DSM-IV criteria. RESULTS: A total of 871 patients were included in the study; 72% were females, and most patients had BMI ≥ 40 kg/m2 (81%). Overall, 55% of the patients were diagnosed with at least one lifetime psychiatric disorder. Binge eating disorder (27.6%), major depressive disorder (16%), bipolar disorder type 2 (15.5%), and panic disorder (16%) were the most common psychiatric diagnoses. Mood disorders showed associations with panic disorder (OR = 2.75, 95% CI = 1.90-3.99, χ2 = 41.85, p = 0.000) and eating disorders (OR = 2.17, 95% CI 1.64-2.88, χ2 = 55.54, p = 0.000). BMI was lower in patients with major depressive disorder (44.9 ± 7.89) than in subjects without mood disorders (46.75 ± 7.99, padj = 0.017). CONCLUSION: Bariatric patients show high rates of psychiatric disorders, especially binge eating and mood disorders. Longitudinal studies are needed to explore the possible influence of such comorbidities on the long-term outcome after bariatric surgery. LEVEL OF EVIDENCE: V, cross sectional descriptive study.

Prevalence and psychiatric comorbidities of night-eating behavior in obese bariatric patients: preliminary evidence for a connection between night-eating and bipolar spectrum disorders.

PURPOSE: The co-occurrence of obesity, eating and mood disorders has been frequently reported in clinical and epidemiological settings. This study aimed to explore the prevalence of night-eating obese patients referred for bariatric surgery and to identify associated psychopathology and psychiatric comorbidity. METHODS: The sample was composed of 121 obese patients consecutively enrolled between November 2010 and May 2012 during psychiatric evaluations for bariatric intervention. Clinical features and psychiatric diagnoses were collected. Night-eating was investigated through the administration of the Night-eating Questionnaires (NEQ) and was defined as the presence of self-reported evening hyperphagia and/or nocturnal ingestions. Binge-eating and purging behaviors and general psychopathology were respectively assessed using the Bulimic Investigatory Test, Edinburgh and the Symptom Checklist-90-Revised. RESULTS: Night-eating was reported by twenty subjects (16.5%). Patients with night-eating behavior were significantly more frequently diagnosed with bipolar spectrum disorders and with comorbid eating and mood disorders in comparison with other patients. Night-eating patients showed significantly more binging/purging behaviors and greater severity of somatization, obsessive-compulsive symptoms, phobic anxiety, psychoticism and sleep disorders. Patients with bipolar disorder type 1 or 2 scored significantly higher than those without mood disorders at NEQ total score, mood/sleep and nocturnal ingestions subscales, but also scored significantly higher than other patients with mood disorders at the latter subscale. CONCLUSION: Patients with evening hyperphagia and/or nocturnal ingestions should be carefully evaluated to detect possible bipolar spectrum disorders and other eating disorders. Prompt management of these conditions should be provided before bariatric interventions. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

Clinical features and predictors of non-response in severe catatonic patients treated with electroconvulsive therapy.

OBJECTIVE: To explore the demographic and clinical features of severe catatonic patients, comparing responders and non-responders to ECT in order to detect possible predictors of non-response. METHODS: This naturalistic study included 59 catatonic inpatients with a diagnosis of mood disorder according to DSM-IV-TR criteria. All patients were treated with bilateral ECT and evaluated before and after ECT course. The response to ECT was defined as a Clinical Global Impression (Improvement subscale) rating 1 'very much improved' or 2 'much improved'. Clinical variables were compared between responders and non-responders; logistic regression was used to predict the probability of non-response, with regard to the symptoms presented by the patients. RESULTS: The response rate was 83.1%. Non-responders (n = 10) to ECT showed neurological comorbidities, treatments with dopamine agonists and anticholinergic drugs, waxy flexibility, and echophenomena more frequently than respondents (n = 49). Echophenomena resulted a significant predictor of non-response in the multivariate analysis. CONCLUSION: In line with previous reports, ECT resulted effective in the vast majority of severe catatonic patients. The association between ECT resistant catatonia and neurological comorbidity, use of dopamine-agonist and anticholinergic medications is consistent with the hypothesis that ECT is more effective in 'top-down' than in 'bottom-up' variant of catatonia.Key pointsCatatonic symptoms are frequently associated with severe and psychotic mood disorders.Electroconvulsive therapy is effective in treating most forms of severe catatonia.Neurological comorbidity and the presence of 'echopraxia/echolalia' could represent predictors of non-response to ECT.

High exposure to pharmacological treatments is associated with limited efficacy of electroconvulsive therapy in bipolar depression.

Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT.

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.

Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD.

Background and Objectives: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. Materials and Methods: One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. Results: Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. Conclusions: ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with "sunny" cyclothymic features might escape the attention of clinicians unless ADHD is present.

Mood disorders comorbidity in obese bariatric patients: the role of the emotional dysregulation.

BACKGROUND: Obese patients seeking bariatric surgery are known to show high rates of mental disorders, mainly mood and eating disorders. The aim of the present study is to evaluate psychiatric comorbidities, affective temperamental dimensions, emotional dysregulation and impulsivity in a sample of obese bariatric patients, exploring the differences between obese patients with and without mood disorders (MD). METHODS: A total of 69 obese patients were consecutively enrolled between March and November 2019 during the presurgical evaluation routinely performed before the bariatric intervention. Sociodemographic and clinical features were collected by psychiatrists during a single consultation. Affective temperaments, emotional dysregulation and impulsivity were also investigated through self-report questionnaires. Epidemiological and clinical variables were compared between patients with and without MD. RESULTS: In our sample, almost 3 out of 4 patients presented a lifetime psychiatric disorder, mainly MD (n=33, 48%), binge eating disorder (BED) (n=34, 49%) and anxiety disorders (n=30, 43%). Compared to N-MD patients, those with MD showed higher rates of psychiatric comorbidity with BED, bulimia and panic disorder. In addition, obese patients with MD showed more frequently cyclothymic, depressive and anxious temperaments, and higher mean scores on the psychometric questionnaires assessing emotional dysregulation and impulsivity compared to obese subjects without MD. LIMITATIONS: the small sample size, the retrospectively assessment of psychiatric disorders and the self-report questionnaires. CONCLUSIONS: A subgroup of obese patients, especially among those with MD, show high emotional dysregulation, affective lability and impulsiveness that could represent suitable substrates for the development of compulsive and addictive eating habits.

Association of treatment facets, severity of manic symptoms, psychomotor disturbances and psychotic features with response to electroconvulsive therapy in bipolar depression.

OBJECTIVES: Clinically useful predictors of response to electroconvulsive therapy (ECT) are warranted, especially in the case of bipolar depression. The aim of this study was to explore the associations between response and its known and putative correlates. METHODS: Six hundred seventy bipolar depressive patients treated with ECT were included in the study. The association between response (CGI-I ≤ 2) and mean seizure duration, number of treatments, age, sex, bipolar subtype, episode duration, HAM-D and YMRS scores, psychomotor disturbances and psychotic symptoms assessed through BPRS-EV were evaluated by means of univariate and multivariate logistic regression models, including quadratic and/or linear effects of continuous variables. RESULTS: Four hundred eighty three patients (72%) were responders. Among known correlates of response, significant quadratic effects were found for seizure duration and number of treatments, while a linear association was confirmed for episode duration. Among putative correlates, severe motor retardation, tension or agitation, hyperactivity and delusions of guilt were significantly associated with response (p<.01) and a significant quadratic effect was found for YMRS score (p<.01). CONCLUSION: Bipolar depressive patients with severe psychomotor disturbances, mood-congruent delusions and severe mixed features are highly responsive to ECT. A significant improvement in response prediction is expected when considering those clinical characteristics.

Factors associated with single versus multiple suicide attempts in depressive disorders.

BACKGROUND: Many risk factors for suicidal behavior have been identified. Much less has been done to associate risk factors with recurrence of suicidal behavior. METHODS: We compared prevalence of 30 potential risk factors among 8496 depressive patient-subjects from the BRIDGE consortium with no (NSA, n = 6267), one (1SA, n = 1123), or repeated (≥2) suicide attempts (RSA, n = 1106). RESULTS: Prevalence of most factors ranked: RSA ≥ 1SA > NSA, with a notable opposite trend for the diagnosis of type II bipolar disorder (BD). Factors independently and significantly more present among RSA than 1SA subjects were: borderline personality, substance abuse, mood-switching with antidepressant treatment, female sex, and unsatisfactory response to antidepressant treatment. There also were notably strong associations of RSA with type I or probable BD and associated factors, including family history of BD, young onset, mixed and psychotic features. LIMITATIONS: Potential effects of treatment on risk of suicidal acts could not be evaluated adequately, as well as associations between levels of suicidal behavior and eventual death by suicide. CONCLUSIONS: In a large cohort of depressive patients, there were significant associations not only with suicidal behavior generally, but also with the intensity of suicide attempts.