Bipolar disorder, comorbid anxiety disorders, gynecomastia and dental pain: case analysis with literature review.

Bipolar disorder with comorbid anxiety disorders frequently requires rational polypharmacy, including use of serotonergic psychotropics. These may result in adverse effects, influencing adherence, complicating treatment and confounding diagnoses. Serotonergic non-adherence is associated with discontinuation syndromes. In this complex case with an on/off/on/off design, both dose-dependent buspirone-induced gynecomastia and buspirone discontinuation syndrome with dental pain are reported. Clinicians and patients should consider these findings to maximise treatment adherence, minimise any unnecessary interventions and address unusual adverse effects. Since patients may not voluntarily disclose specific adverse effects and often do not acknowledge non-adherence, clinician-directed questions are required. This case further emphasises the importance of medication and symptom timelines to guide determination of causation for adverse effects. Although findings from this case cannot be generalised, they suggest the need for continued clinician and patient education, as well as the benefit from detailed case reports. DECLARATION OF INTEREST: None.

Trastornos de bipolares y comorbilidades - consideraciones éticas en deportes / Bipolar disorders and comorbid conditions - Ethical considerations in sports

Introducción: El objetivo de la intervención farmacológica es el resultado terapéutico: máxima eficacia con mínimos efectos adversos. Esto resulta difícil a la hora de tratar el trastorno bipolar, debido a las comorbilidades y/o fármacos complementarios necesarios para abordar los efectos adversos. La polifarmacia racional óptima puede maximizar el resultado terapéutico, aunque podría crear cuestiones éticas en los deportes competitivos. El Código Mundial Antidopaje (WADC) y la Lista de Sustancias Prohibidas de la Agencia Mundial Antidopaje, publicada anualmente, tienen como objetivo disuadir y sancionar a los atletas que utilicen agentes para mejorar el rendimiento, y promover un marco de igualdad para todos los competidores. Este documento presenta tres ejemplos hipotéticos (TDAH/temblor secundario al litio/dolor) en los que la contravención no deliberada de la Lista de Sustancias Prohibidas derivaría en descalificación por violación de la norma antidopaje sin aprobación de las Exenciones por Uso Terapéutico (TUEs). Método: Análisis de caso hipotético con revisión de la literatura. Resultados: TDAH Comórbido: la Lista de Sustancias Prohibidas excluye los psicoestimulantes (metilfenidato/anfetaminas) en la competición (S6) pero permite guanfacina/atomoxetina. En los casos en que los psicoestimulantes constituyeran un tratamiento eficaz para el TDAH en los atletas con trastorno bipolar, a diferencia de guanfacina/atomoxetina, estos pacientes-atletas deberán presentar TUEs, junto con la certificación y documentación de respaldo del clínico. Temblor secundario al Litio: a menudo se prescriben beta-bloqueantes para controlar el temblor secundario al litio, pero que no están autorizados para deportes específicos (P2). En caso de que los fármacos alternativos (primidona) resulten ineficaces, serán necesarias las TUEs. Dolor: el manejo del dolor crónico es difícil en atletas, ya que los analgésicos narcóticos (S7) y cannabinoides (S8) están prohibidos en la competición. Cuando el dolor comórbido no se controla con fármacos autorizados, son necesarias las TUEs. Conclusión: Los pacientes-atletas con trastorno bipolar y comorbilidades precisan enfoques holísticos, con reconocimiento tanto del WADC como de la Lista de Sustancias Prohibidas. Los atletas deberían realizar un listado de todos los fármacos incluyendo diagnósticos/obtener TUEs/verificar el estado de la medicación propuesta (prohibido/restringido/permitido) con las Federaciones Internacionales adecuadas y/u Organizaciones Olímpicas. Los clínicos deberán ser conocedores de estas cuestiones a la hora de tratar a los pacientes-atletas

Introduction: The goal of pharmacologic intervention is therapeutic outcome: maximal efficacy with minimal adverse effects. In treating bipolar disorder, this may be complicated by comorbidities and/or adjunctive medications required to address adverse effects. Optimal rational polypharmacy may maximize therapeutic outcome yet could create ethical issues in competitive sports. The World Anti-Doping Code (WADC) and yearly published World Anti-Doping Agency Prohibited List are intended to deter and sanction athletes using performance-enhancing agents while promoting an even playing field for all competitors. This paper presents three hypothetical examples (ADHD/lithium-tremor/pain) wherein unintended Prohibited List contravention would result in doping violation disqualifications without approved Therapeutic Use Exemptions (TUEs). Method: Hypothetical case analyses with literature review. Results: Comorbid ADHD: the Prohibited List precludes psychostimulants (methylphenidate/amphetamines) in competition (S6) but permits guanfacine/atomoxetine. When psychostimulants effectively treat ADHD in athletes with bipolar disorder but guanfacine/atomoxetine do not, these patient-athletes, with clinician’s certification and supportive documentation, should file TUEs. Lithium-tremor: beta-blockers are frequently prescribed to control lithium-tremor but are not permitted for specific sports (P2). If alternatives (primidone) are ineffective, TUEs are indicated. Pain: chronic pain management is difficult in athletes as narcotic analgesics (S7) and cannabinoids (S8) are prohibited in competition. When comorbid pain is not controlled with approved medications, TUEs are required. Conclusion: Patient-athletes with bipolar disorder and comorbidities require holistic approaches with appreciation of both the WADC and Prohibited List. Athletes should list all medications with diagnoses/obtain TUEs/verify proposed medication status (banned/restricted/permitted) with appropriate International Federations and/or Olympic organizations. Clinicians should be cognizant of these issues when treating patient-athletes

Lamotrigine-induced sexual dysfunction and non-adherence: case analysis with literature review.

BACKGROUND: Optimal anti-epileptic drug (AED) treatment maximises therapeutic response and minimises adverse effects (AEs). Key to therapeutic AED treatment is adherence. Non-adherence is often related to severity of AEs. Frequently, patients do not spontaneously report, and clinicians do not specifically query, critical AEs that lead to non-adherence, including sexual dysfunction. Sexual dysfunction prevalence in patients with epilepsy ranges from 40 to 70%, often related to AEDs, epilepsy or mood states. This case reports lamotrigine-induced sexual dysfunction leading to periodic non-adherence. AIMS: To report lamotrigine-induced sexual dysfunction leading to periodic lamotrigine non-adherence in the context of multiple comorbidities and concurrent antidepressant and antihypertensive pharmacotherapy. METHOD: Case analysis with PubMed literature review. RESULTS: A 56-year-old male patient with major depression, panic disorder without agoraphobia and post-traumatic stress disorder was well-controlled with escitalopram 20 mg bid, mirtazapine 22.5 mg qhs and alprazolam 1 mg tid prn. Comorbid conditions included complex partial seizures, psychogenic non-epileptic seizures (PNES), hypertension, gastroesophageal reflux disease and hydrocephalus with patent ventriculoperitoneal shunt that were effectively treated with lamotrigine 100 mg tid, enalapril 20 mg qam and lansoprazole 30 mg qam. He acknowledged non-adherence with lamotrigine secondary to sexual dysfunction. With lamotrigine 300 mg total daily dose, he described no libido with impotence/anejaculation/anorgasmia. When off lamotrigine for 48 h, he described becoming libidinous with decreased erectile dysfunction but persistent anejaculation/anorgasmia. When off lamotrigine for 72 h to maximise sexual functioning, he developed auras. Family confirmed patient's consistent monthly non-adherence for 2-3 days during the past year. CONCLUSIONS: Sexual dysfunction is a key AE leading to AED non-adherence. This case describes dose-dependent lamotrigine-induced sexual dysfunction with episodic non-adherence for 12 months. Patient/clinician education regarding AED-induced sexual dysfunction is warranted as are routine sexual histories to ensure adherence. DECLARATION OF INTEREST: No financial interests. K.R.K. is Editor of BJPsych Open; he took no part in the peer-review of this work. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Sex differences in extinction recall in posttraumatic stress disorder: a pilot fMRI study.

Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology.