Polypharmacy or medication washout: an old tool revisited

There has been a rapid increase in the use of polypharmacy in psychiatry possibly due to the introduction of newer drugs, greater availability of these newer drugs, excessive confidence in clinical trial results, widespread prescribing of psychotropic medications by primary care, and pressure to augment with additional medications for unresolved side effects or greater efficacy. Even the new generation of medications may not hold significant advantages over older drugs. In fact, there may be additional safety risks with polypharmacy being so widespread. Washout, as a clinical tool, is rarely done in medication management today. Studies have shown that augmenting therapy with additional medications resulted in 9.1%–34.1% dropouts due to intolerance of the augmentation, whereas studies of medication washout demonstrated only 5.9%–7.8% intolerance to the washout procedure. These perils justify reconsideration of medication washout before deciding on augmentation. There are unwarranted fears and resistance in the medical community toward medication washout, especially at the moment a physician is trying to decide whether to washout or add more medications to the treatment regimen. However, medication washout provides unique benefits to the physician: it establishes a new baseline of the disorder, helps identify medication efficacy from their adverse effects, and provides clarity of diagnosis and potential reduction of drug treatments, drug interactions, and costs. It may also reduce overall adverse events, not to mention a potential to reduce liability. After washout, physicians may be able to select the appropriate polypharmacy more effectively and safely, if necessary. Washout, while not for every patient, may be an effective tool for physicians who need to decide on whether to add potentially risky polypharmacy for a given patient. The risks of washout may, in some cases, be lower and the benefits may be clearly helpful for diagnosis, understanding medication effects, the doctor/patient relationship, and safer use of polypharmacy if indicated

Euthymic Patients with Bipolar Disorder Show Decreased Reward Learning in a Probabilistic Reward Task

Background: Bipolar disorder (BPD) features cycling mood states ranging from depression to mania with intermittent phases of euthymia. Bipolar disorder subjects often show excessive goal-directed and pleasure-seeking behavior during manic episodes and reduced hedonic capacity during depressive episodes, indicating that BPD might involve altered reward processing. Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms. Methods: Eighteen medicated BPD subjects and 25 demographically matched comparison subjects performed a probabilistic reward task. To identify putative dysfunctions in reward processing irrespective of mood state, primary analyses focused on euthymic BPD subjects (n = 13). With signal-detection methodologies, response bias toward a more frequently rewarded stimulus was used to objectively assess the participants' propensity to modulate behavior as a function of reinforcement history. Results: Relative to comparison subjects, euthymic BPD subjects showed a reduced and delayed acquisition of response bias toward the more frequently rewarded stimulus, which was partially due to increased sensitivity to single rewards of the disadvantageous stimulus. Analyses considering the entire BPD sample revealed that reduced reward learning correlated with self-reported anhedonic symptoms, even after adjusting for residual manic and anxious symptoms and general distress. Conclusions: The present study provides preliminary evidence indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.Psycholog

Major depression in patients with non-cardiac chest pain: Who is going to treat?

OBJETIVO: Investigar a presença de transtornos psiquiátricos em pacientes com dor torácica de origem não cardíaca que não respondem aos tratamentos regulares. MÉTODO: Dezoito pacientes com dor torácica sem origem cardíaca e considerados por seus clínicos como não respondentes aos tratamentos regulares instituídos foram avaliados por um psiquiatra treinado. As entrevistas foram realizadas com base no Present State Examination e os diagnósticos psiquiá-tricos, de acordo com os critérios do Manual de Diagnóstico e Estatística da Associação Psiquiátrica Americana, 3ª Edição Revisada (DSM-III-R). RESULTADOS: Depressão maior no momento da avaliação foi diagnosticada em 6 (30%) pacientes, somatização em 1 (6%) e transtorno do pânico em 1 (6%) paciente. Sete pacientes estavam recebendo antidepressivos tricíclicos com doses < 75 mg/dia. CONCLUSÕES: A baixa dose de ADTs usadas para o tratamento da dor nesses pacientes pode ter melhorado parcialmente os sintomas depressivos, tornando mais difíceis o diagnóstico e o tratamento apropriado(s) da depressão e, assim, contribuindo para a persistência da dor e outras queixas. As futuras pesquisas deverão focalizar a eficácia do tratamento da depressão nesses pacientes e o impacto deste no alívio da dor torácica não cardíaca.OBJECTIVE: To investigate the presence of psychiatric disorders in patients with chest pain not responsive to treatment. METHOD: We evaluated 18 patients judged by their physicians to have a chest pain not responsive to usual treatment, which included anti-pain medicines and investigation and treatment of possible etiological causes such as coronary artery disease, and gastroesophageal reflux disease. A psychiatrist interviewed the patients using the Present State Examination and made the diagnosis based on the DSM-III-R criteria. Current major depression was diagnosed in 6 (30%) patients, somatization in 1 (6%) and panic disorder in 1 (6%) patient. Seven patients were receiving tricyclics antidepressant with doses > 75 mg/day. DISCUSSION: Patients were receiving doses of tricyclics antidepressants efficacious for pain but not for major depression. It is possible that the low dose of antidepressants used to treat pain may partially ameliorate depressive symptoms, making the appropriate diagnosis and treatment of major depression even more difficult, consequently contributing to the persistence of pain and other complains. Considering the wide alternatives to effectively treat depression, a focus on detection and treatment of major depression in patients with chest pain is warranted by clinicians and researchers

The association of major depressive episode and personality traits in patients with fibromyalgia

INTRODUCTION: Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia. OBJECTIVE: The authors investigated the association between a current major depressive episode and temperament traits (e.g., harm avoidance). METHOD: A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale. RESULTS: A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found. CONCLUSIONS: The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients

Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.Psycholog

Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.Psycholog

Depressão maior em pacientes com dor torácica não cardíaca: Quem vai tratar?

OBJECTIVE: To investigate the presence of psychiatric disorders in patients with chest pain not responsive to treatment. METHOD: We evaluated 18 patients judged by their physicians to have a chest pain not responsive to usual treatment, which included anti-pain medicines and investigation and treatment of possible etiological causes such as coronary artery disease, and gastroesophageal reflux disease. A psychiatrist interviewed the patients using the Present State Examination and made the diagnosis based on the DSM-III-R criteria. Current major depression was diagnosed in 6 (30%) patients, somatization in 1 (6%) and panic disorder in 1 (6%) patient. Seven patients were receiving tricyclics antidepressant with doses >; 75 mg/day. DISCUSSION: Patients were receiving doses of tricyclics antidepressants efficacious for pain but not for major depression. It is possible that the low dose of antidepressants used to treat pain may partially ameliorate depressive symptoms, making the appropriate diagnosis and treatment of major depression even more difficult, consequently contributing to the persistence of pain and other complains. Considering the wide alternatives to effectively treat depression, a focus on detection and treatment of major depression in patients with chest pain is warranted by clinicians and researchers.OBJETIVO: Investigar a presença de transtornos psiquiátricos em pacientes com dor torácica de origem não cardíaca que não respondem aos tratamentos regulares. MÉTODO: Dezoito pacientes com dor torácica sem origem cardíaca e considerados por seus clínicos como não respondentes aos tratamentos regulares instituídos foram avaliados por um psiquiatra treinado. As entrevistas foram realizadas com base no Present State Examination e os diagnósticos psiquiá-tricos, de acordo com os critérios do Manual de Diagnóstico e Estatística da Associação Psiquiátrica Americana, 3ª Edição Revisada (DSM-III-R). RESULTADOS: Depressão maior no momento da avaliação foi diagnosticada em 6 (30%) pacientes, somatização em 1 (6%) e transtorno do pânico em 1 (6%) paciente. Sete pacientes estavam recebendo antidepressivos tricíclicos com doses < 75 mg/dia. CONCLUSÕES: A baixa dose de ADTs usadas para o tratamento da dor nesses pacientes pode ter melhorado parcialmente os sintomas depressivos, tornando mais difíceis o diagnóstico e o tratamento apropriado(s) da depressão e, assim, contribuindo para a persistência da dor e outras queixas. As futuras pesquisas deverão focalizar a eficácia do tratamento da depressão nesses pacientes e o impacto deste no alívio da dor torácica não cardíaca