Suicide in a large population of former psychiatric inpatients.

AIMS: The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM-IV diagnoses. METHODS: We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35-year period in a private hospital setting. We collected sociodemographic, clinical and temperamental data. RESULTS: Ninety-six patients from the sample committed suicide. There were no sex differences in suicide completion and no differences between major psychiatric disorders, but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression. Shorter-term treatment with lithium and anticonvulsants, longer-term treatment with antidepressants, history of suicide attempts, suicidal thinking, and single status positively predicted completed suicide. Suicide tended to occur after a mean period of about 14 years of duration of disease. Patients' symptoms during the period preceding suicide were assessed through interviewing patients' physicians or family members. Symptoms occurring in >10% of cases were, in decreasing order, inner tension, racing/crowded thoughts, aggressive behavior, guilt, psychomotor agitation, persecutory ideation, anxiety, and hallucinations. Surprisingly, cyclothymic temperament was less associated with completed suicide as compared to other temperaments. CONCLUSIONS: Suicide is likely to occur in a milieu of agitation, mixed anxiety and depression, and psychosis. Longer-term mood stabilizer treatment may reduce the rate of completed suicide.

Early clinical predictors of long-term morbidity in major depressive disorder.

AIMS: To identify early clinical factors predictive of later morbidity in major depressive disorder (MDD). METHODS: We analysed factors associated with long-term depressive morbidity (%-time ill) between a first-lifetime major depressive episode and last follow-up of 116 adults diagnosed with DSM-IV major depressive disorder. Bivariate comparisons were followed by multivariable linear regression modelling. RESULTS: Three factors were independently associated with an average of 25%-time-depressed over 17 years at risk: (a) agitated-mixed, or psychotic features in initial major depressive episodes, (b) anxiety syndromes prior to a first-lifetime major depressive episode, and (c) anxiety symptoms in childhood. CONCLUSION: Early anxiety symptoms and syndromes and agitated-mixed or psychotic initial depressive episodes predicted more long-term depressive morbidity in MDD.

Psychopathological characteristics and adverse childhood events are differentially associated with suicidal ideation and suicidal acts in mood disorders.

BACKGROUND: Depression is an important risk factor for suicide. However, other dimensions may contribute to the suicidal risk and to the transition from ideas to acts. We aimed to test the relative involvement of hopelessness, temperament, childhood trauma, and aggression in suicide risk in a large sample of patients with mood disorders. METHODS: We assessed 306 patients with major depressive and bipolar disorders for clinical characteristics including hopelessness, temperament, childhood trauma, and aggression. We tested their associations with suicidal ideation and acts using standard univariate/bivariate methods, followed by multivariate logistic regression models. RESULTS: In multivariate analyses, the loss of expectations subscore of the hopelessness scale was associated with lifetime suicidal ideation but not suicide attempt. Childhood emotional abuse, severity of current depression, and female gender were associated with lifetime suicide attempts, whereas hyperthymic temperament was protective. Only hyperthymic temperament differentiated patients with a history of suicidal ideas vs. those with a history of suicide attempt. CONCLUSIONS: Findings support the association of hopelessness with suicidal ideation and point to considering in suicidal acts not only depression, but also childhood emotional abuse, hyperthymic temperament, and gender.

Free Interval Duration: Clinical Evidence of the Primary Role of Excitement in Bipolar Disorder.

BACKGROUND: Cyclicity is the essential feature of Bipolar disorder, but the effect of different cycle patterns on the clinical features is poorly understood. Moreover, no studies investigated the relationship between mania and depression inside the manic-depressive cycle. OBJECTIVE: The aim of this study is to verify the presence of a relationship between the manic and the depressive phase during the course of bipolar disorder. METHOD: 160 consecutive patients with BD type I were recruited and followed for a mean period of 10 years. During the follow-up period, four types of euthymic phases were collected: free intervals present between a depressive and a manic/hypomanic episode (D-M); free intervals present between a manic/hypomanic and a depressive episode (M-D); free intervals present between two depressive episodes (D-D); free intervals present between two manic/hypomanic episodes (M-M). One-way ANOVA using the groups as independent variable and the duration of the free intervals as dependent variables was used. Furthermore, ANOVA was followed by Fisher's Protected Least Significant Difference post-hoc test to measure between-group differences. RESULTS: M-D-free interval phases were shorter than D-M-free intervals. M-D intervals were the shortest ones, the D-D and D-M did not differ, and the M-M were the longest. CONCLUSION: The strict temporal link between manic and depressive phases supports the idea that the manic-depressive cycle usually begins with a manic episode, and that the subsequent depression is often the consequence of subsiding mania.

Child and Adolescent Clinical Features Preceding Adult Suicide Attempts.

The objective of this study was to identify the predictive value of juvenile factors for adult suicidal behavior. We reviewed clinical records to compare factors identified in childhood and adolescence between adult suicidal versus nonsuicidal major affective disorder subjects. Suicide attempts occurred in 23.1% of subjects. Age-at-first-symptom was 14.2 vs. 20.2 years among suicidal versus nonsuicidal subjects (p < 0.0001). More prevalent in suicidal versus non-suicidal subjects by multivariate analysis were: depressive symptoms, hyper-emotionality, younger-at-first-affective-episode, family suicide history, childhood mood-swings, and adolescence low self-esteem. Presence of one factor yielded a Bayesian sensitivity of 64%, specificity of 50%, and negative predictive power of 86%. Several juvenile factors were associated with adult suicidal behavior; their absence was strongly associated with a lack of adult suicidal behavior.

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters.

BACKGROUND: Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. METHODS: Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8-48 (mean 18) years and aged 20-89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea-nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. RESULTS: Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years. LIMITATIONS: Control data for age-matched subjects not exposed to lithium were lacking. CONCLUSIONS: Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

Depressive mixed states: A reappraisal of Koukopoulos' criteria.

BACKGROUND: Mixed states have been a fundamental part of Kraepelin׳s conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression. METHODS: We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos׳ first description of depressive mixed syndrome in 1992. RESULTS: The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture. LIMITATIONS: Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos. CONCLUSIONS: Koukopoulos׳ proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.

The sustained mood-stabilizing effect of memantine in the management of treatment resistant bipolar disorders: findings from a 12-month naturalistic trial.

BACKGROUND: We have recently provided preliminary clinical observations indicating that memantine, as augmenting agent, was associated with a meaningful antimanic and mood-stabilizing effect in treatment-resistant bipolar disorders. To further investigate the therapeutic and prophylactic action of the drug we administered memantine, as augmenting agent, to 40 treatment-resistant bipolar disorder patients, monitored and evaluated for 12 months. METHODS: The sample population encompassed 40 treatment-resistant bipolar disorder patients monitored for 12 months. Memantine, at the dose of 10-30 mg/day, was added to the ongoing treatment, which was left unmodified. The severity of the patients' condition before memantine and the changes after memantine addition were evaluated on the Clinical Global Impression Bipolar (CGI-BP) Overall Bipolar Illness Scale. The severity of patients' condition was scored before memantine and the change was evaluated after memantine addition at 6 and 12 months. LIMITATIONS: The present study has the limitations of an open clinical study and the observed effects require testing in a blinded, randomized, controlled trial which is planned. RESULTS: The average CGI-BP score of the patients was 6.7 (SD=0.58, range: 5-7) before the addition of memantine. After 6 months of memantine treatment, 72.5% of patients were very much or much improved. Among the rapid cyclers 68.4% of patients reached stability, defined by the absence of recurrences. Patients very much or much improved were 72.5% at 12 months; while 12.5% discontinued memantine or were lost to follow-up. CONCLUSIONS: The results confirm our previous observations and strongly suggest that memantine, as augmenting agent, was associated with a clinically substantial antimanic and sustained mood-stabilizing effect, with excellent safety and tolerability profile.

Episodes of mood disorders in 2,252 pregnancies and postpartum periods.

OBJECTIVE: The risks of major affective episodes during pregnancy and during the postpartum period have rarely been compared in large samples across diagnoses. The authors hypothesized that perinatal episodes would mainly be depressive, would occur more in the postpartum than the prenatal period, and would be more prevalent with bipolar than unipolar depressive disorders. METHOD: The authors pooled clinical information on 2,252 pregnancies of 1,162 women with clinically treated DSM-IV bipolar I disorder (479 pregnancies/283 women), bipolar II disorder (641/338), or recurrent major depressive disorder (1,132/541) to compare rates of affective episode types by diagnosis during pregnancy and the postpartum period and to identify risk factors. RESULTS: Among women with bipolar disorder, 23% had illness episodes during pregnancy and 52% during the postpartum period. Among women with unipolar depression, 4.6% had illness episodes during pregnancy and 30% during the postpartum period. Based on exposure-adjusted risk per pregnancy, episodes were 3.5 times more prevalent during the postpartum period than during pregnancy, and the risk was consistently higher with bipolar disorder. Depression was the most frequent morbidity during and following pregnancy. In multivariate modeling, factors associated with affective episodes in pregnancy, in descending order, were younger age at onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Postpartum episodes were associated with younger age at onset, illness during pregnancy, bipolar disorder, fewer children, and more education. Moreover, pregnancy was less likely and perinatal episodes more likely if diagnosis preceded a first pregnancy. First lifetime episodes occurred in the perinatal period in 7.6% of cases. CONCLUSIONS: Among women with major affective disorders, illness risk was much greater during the postpartum period than during pregnancy. Illness mainly involved depression and was strongly associated with younger age at illness onset, bipolar disorder, and high lifetime occurrence rates. The relative risk during pregnancy compared with nonpregnant periods remains uncertain.