Frye, Mark

Abstract Background Anxiety disorders (ANX) affect 30–60% of individuals with bipolar disorder (BD), yet limited research has systematically examined clinical characteristics and treatment patterns in this comorbid population. This study investigated demographic, clinical, and pharmacotherapeutic differences between individuals with BD with and without comorbid ANX. Methods Cross-sectional data from 2,225 adults with BD enrolled in the Mayo Clinic Bipolar Disorder Biobank were analyzed. Participants were assessed for comorbid ANX, demographics, clinical characteristics, medication use, and treatment response using the Alda-A scale. Results Overall, 61% (n = 1,366) had comorbid ANX. Individuals with BD + ANX were younger (40.4 vs. 43.6 years, p < 0.001), more likely female (66.6% vs. 54.8%, p < 0.001), and exhibited higher rates of rapid cycling (64.2% vs. 45.2%, p < 0.001), suicide attempts (40.4% vs. 24.8%, p < 0.001), substance use disorders (63.5% vs. 54.8%, p < 0.001), and somatic comorbidities (MCIRS: 6.68 vs. 5.42, p < 0.001). Pharmacotherapeutically, BD + ANX individuals were less likely to receive lithium (37.1% vs. 47.8%, p = 0.005) and valproic acid (21.7% vs. 29.6%, p = 0.047), but more likely to receive antidepressants (53.8% vs. 39.5%, p < 0.001), benzodiazepines (39.9% vs. 26.6%, p < 0.001), and gabapentinoids (8.5% vs. 4.5%, p < 0.001). Notably, 17.3% of BD + ANX individuals received antidepressants without mood stabilizer coverage. Treatment response (Alda-A) scores were significantly lower in BD + ANX for lithium (4.91 vs. 6.05, p < 0.001), mood-stabilizing anticonvulsants (5.09 vs. 6.22, p < 0.001), and second-generation antipsychotics (4.67 vs. 5.73, p < 0.001). Similar patterns were observed in both BD-I and BD-II subtypes. Conclusions Individuals with BD + ANX represent a more severely affected subgroup with distinct prescribing patterns favoring antidepressants over mood stabilizers and attenuated mood stabilizers response. These findings highlight the need for anxiety-informed treatment algorithms recognizing anxiety comorbidity as a negative prognostic factor.

AbstractBackgroundLithium is regarded as a first‐line treatment for bipolar disorder (BD), but partial response and non‐response commonly occurs. There exists a need to identify lithium non‐responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response.MethodsThe PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse.ResultsA total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness.ConclusionsIn this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.

Abstract The relationship of personality disorder (PD) psychopathology to the course of bipolar disorder remains inadequately described. After giving informed consent, more than 782 outpatients with bipolar disorder rated themselves on the 99-item Personality Disorder Questionnaire, Version 4 (PDQ4) when depressed or euthymic. They also rated six poor prognosis factors (PPFs). The relationships of the PPFs to the total PDQ4 score were examined by a linear regression. Even after correcting for the higher PDQ4 scores observed when patients were suffering depression, the PDQ4 was significantly related to a history of child abuse, early age of onset, an anxiety disorder comorbidity, rapid cycling, and 20 or more previous episodes, but not substance abuse. The data suggest close relationships between the total burden of PD psychopathology and correlates of an adverse outcome of bipolar disorder. The nature of this of association and approaches to treatment of comorbid PD remain to be further explored.

AbstractObjectivesA high incidence of Axis II personality disorders is described in patients with bipolar disorder; however, their relationship to mood state remains uncertain.MethodsA total of 966 outpatients with bipolar disorder gave informed consent and filled out the Personality Disorder Questionnaire, 4th edition (PDQ4) and a questionnaire on demographics and course of illness prior to Bipolar Treatment Outcome Network entry at average age 41 years. Patients were rated at each visit for depression on the Inventory of Depressive Symptoms‐Clinician version (IDS‐C) and for mania on the Young Mania Rating Scale (YMRS). In a subgroup, the PDQ4 was retaken during periods of depression and euthymia.ResultsPatients met criteria for most personality disorders at a much higher rate when they took the PDQ4 while depressed compared to while euthymic, and scores were significantly related to the severity of depression (IDS) and of mania (YMRS) assessed within 2 weeks of taking the PDQ. Even when euthymic, more than quarter to half of the patients met criteria for a cluster A, B or C personality disorder.ConclusionsA wide range of personality disorders occur in bipolar patients, but are highly dependent on filling out the form while depressed compared to while euthymic. How this relates to having a personality disorder assessed using a structured clinical interview remains to be tested. However, higher PDQ4 scores are related to an earlier age of onset of bipolar disorder and other factors portending a more difficult course of bipolar disorder, and the optimal treatment of these patients remains to be illuminated.