Prescribing Tamoxifen in Patients With Mood Disorders: A Systematic Review of Potential Antimanic Versus Depressive Effects.

PURPOSE/BACKGROUND: Tamoxifen is a selective estrogen receptor modulator widely used for treatment and prevention of estrogenic receptor-positive breast cancer. Tamoxifen is an object of growing interest in psychopharmacology as an antimanic drug, because it inhibits the protein kinase C, a molecular target of bipolar disorder. Consistently, the potential depressive effect of tamoxifen has been repeatedly reported. METHODS/PROCEDURES: This article systematically reviews studies examining tamoxifen impact on mood, exploring either its potential therapeutic use as antimanic agent or its potential depressive effect. FINDINGS: Eight studies explored tamoxifen antimanic properties, all, but one, reported a rapid and efficacious antimanic action. As to the depressive effect, 9 cohort studies emerged among which 4 pointed out an increased risk of depression. Seven case reports described the onset or exacerbation of depressive episodes besides 1 case series study reported a high rate of depressive symptoms. In addition, 1 case report study described a tamoxifen-induced manic episode. IMPLICATIONS/CONCLUSIONS: The present review highlights tamoxifen treatment as a possible trigger of mood symptoms onset or exacerbation in vulnerable patients. Accordingly, patients with a history of mood disorders may require a close clinical surveillance during tamoxifen use. At the same time, the use of tamoxifen as an antimanic agent in psychiatric settings requires caution, as available evidence came from small-sample studies with short observation time. More studies are needed to define how long-term tamoxifen use may affect the course of bipolar disorder.

Interpersonal Problematic Areas in Liaison Psychiatry: A Feasibility Study.

OBJECTIVE: Interpersonal Psychotherapy (IPT) model, with its four problematic areas of grief, deficit, role transition and role dispute, provides a useful frame of reference for a quick case formulation. We aimed at applying the IPT problematic areas assessment in a sample of patients from a liaison psychiatry setting. METHODS: One-hundred and twenty-nine hospitalized patients of both sexes, aged between 18 and 80 years were interviewed. The 'Interpersonal Problem Areas Rating Scale' (IPARS) was used to detect the interpersonal focuses. RESULTS: IPARS problematic areas were identified in the 76% of the sample (n=98). Grief and role transition, interpersonal deficits and role disputes were, respectively, the most frequently (43.4 and 42.6%, respectively) and the less frequently described focuses (14 and 11.6%). Moreover, 31 patients (24%) showed no problem areas related to current symptomatology. CONCLUSIONS: The IPT model has proved to be an easy-to-use tool, able to guide the psychological interview and allowing the collection of information from an interpersonal perspective in a short time, although no specific focuses were detected as related to current psychological distress in around 25% of the sample.

Suicidality and Illness Course Worsening in a Male Patient with Bipolar Disorder during Tamoxifen Treatment for ER+/HER2+ Breast Cancer.

PURPOSE: Tamoxifen is a selective estrogenic receptor modulator (SERM) drug. In addition to its common use in breast cancer ER+, Tamoxifen has been object of growing interest in psychiatry as antimanic drug. At the same time, clinical concerns about Tamoxifen's depressogenic effect have been repeatedly raised even without reaching univocal conclusions. We discuss the case of a 45-year-old-male with a diagnosis of Bipolar Disorder type II, treated with Tamoxifen as relapse prevention treatment after surgery for a ER+/HER2+ breast cancer. The patient required two psychiatric admissions in a few-month time span since he showed a progressive worsening of both depressive and anxiety symptoms, with the onset of delusional ideas of hopelessness and failure up to suicidal thoughts. The clinical picture showed poor response to treatment trials based on various associations of mood-stabilising, antidepressants, and antipsychotic drugs. During the second hospitalization, after a multidisciplinary evaluation, the oncologists agreed on Tamoxifen discontinuation upon the severity of the psychiatric condition. The patient underwent a close oncological and psychiatric follow-up during the following 12 months. METHODS: Psychiatric assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAM-D), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). All questionnaires were administered at the time of the second hospitalization and in a one-year follow-up. RESULTS: Suicidal ideation fully remitted and depressive symptoms markedly and rapidly improved in the aftermath of Tamoxifen discontinuation. The symptomatological improvement remained stable across one-year follow-up. CONCLUSIONS: Male patients with a mood disorder history constitute a high-risk group as to Tamoxifen psychiatric side effects. The onset or worsening of depressive symptoms or suicidality should be carefully addressed and promptly treated, and clinicians should be encouraged to consider the possibility of discontinue or reduce Tamoxifen therapy after a multidisciplinary evaluation.

Predictors of Suicidal Ideation and Preparatory Behaviors in Individuals With Bipolar Disorder: The Contribution of Chronobiological Dysrhythmicity and Its Association With Hopelessness.

OBJECTIVE: To examine the role of chronobiological dysrhythmicity in suicidal ideation and behaviors and its relation with hopelessness. METHODS: One hundred twenty-seven patients (77 females, mean age of 47.4 ± 12.5 years) with a major depressive episode and bipolar disorder (BD) type I or II (according to Structured Clinical Interview for DSM-5 assessment) were recruited in 2019 and assessed for depressive and manic symptoms (Beck Depression Inventory-II, Young Mania Rating Scale) and with the Biological Rhythms Interview of Assessment in Neuropsychiatry, Beck Hopelessness Scale, and Scale for Suicide Ideation. Univariate regression and mediation analyses were performed. RESULTS: Forty-one patients (32.3%) showed clinically significant suicidal ideation and were more frequently affected by BD type I (P = .029) with mixed features (P = .022). Compared to nonsuicidal individuals, they had significantly more depressive symptoms (P = .019), higher emotional component of hopelessness (P = .037), and higher dysrhythmicity of sleep (P = .009), activities (P = .048), and social life (P = .019). Passive and active suicidal ideation and suicidal plans were best predicted by dysrhythmicity of sleep and social life. Dysrhythmicity of sleep and social life mediated the direct effect of depressive symptoms on passive and active suicidal ideation and also of active ideation on suicidal plans. The emotional component of hopelessness was related to dysrhythmicity of social life and mediated its effect on suicidal plans (P = .010). CONCLUSIONS: Chronobiological alterations directly contributed to passive and active suicidal ideation and to suicidal preparation, with a key role of dysrhythmicity of sleep, activities, and social life. Chronobiological alterations also impacted the emotional component of hopelessness, hence indirectly contributing to suicidal ideations and plans. These findings call for the systematic screening of these dysrhythmicity dimensions when considering suicidal risk in individuals with BD.

Association between affective temperaments and mood features in bipolar disorder II: The role of insomnia and chronobiological rhythms desynchronization.

BACKGROUND: Bipolar disorders are complex disorders involving the interaction of multiple factors. Affective temperaments, insomnia, and chronobiological rhythms desynchronization may all contribute to bipolar disorder. Since there is a paucity of research examining this topic we aimed to study how they are interrelated and collectively associated with clinical features of bipolar disorder. METHOD: One-hundred patients with Bipolar Disorder type II depressive episode with and without mixed features were recruited and compared. Subjects were evaluated with SCID -5, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), the Insomnia Severity Index (ISI), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) while evaluating depressive (Beck Depression Inventory-BDI-II) and manic (Young Mania Rating Scale-YMRS) symptoms. Logistic regression and mediation analyses were conducted. RESULTS: Subjects with mixed features showed a higher scores in both insomnia and chronobiological rhythms scores. When considering affective temperaments not only depressive, cyclothymic and irritable temperaments predicted mood symptoms but also insomnia (depressive symptoms O.R. 4.17, p = 0.043) and chronobiological sleep de-synchronization (manic symptoms O.R. 8.69, p = 0.001). Insomnia symptoms and chronobiological alterations mediated the association between affective temperaments and mood symptoms. LIMITATIONS: the cross-sectional design limited any causal interpretation. CONCLUSION: Subjects with mixed features showed a greater severity of insomnia and chronobiological rhythm de-synchronization compared to subjects without. Insomnia and chronobiological alterations may contribute to mood disorders together with affective temperaments in a complex interplay also mediating their effect on mood. Preventive strategies for bipolars should also act on the dysregulation of sleep and circadian rhythms.