A Single-Blind Randomized Comparison of Lithium and Lamotrigine as Maintenance Treatments for Managing Bipolar II Disorder.

PURPOSE/BACKGROUND: No study to date has compared lithium and lamotrigine as maintenance mood stabilizers for bipolar II disorder. The aim of this study was to evaluate and compare these two medications in terms of their maintenance efficacy and side effect profile, thus evaluating their comparative cost/benefit profile. METHODS/PROCEDURES: Forty-four subjects with a newly diagnosed bipolar II disorder were randomly assigned to receive either lithium or lamotrigine treatment in a 20-week single-blinded study. Subjects received either slow-release lithium progressively up-titrated to achieve a serum level of 0.8 mEq/L, or lamotrigine increased progressively to a maintenance dose of 200 mg/d. Our primary outcome measure examined daily data on hypomanic and depressive symptoms. Secondary measures evaluated hypomanic and depressive symptom severity, global functioning, and global improvement in hypomanic and depressive symptoms. FINDINGS/RESULTS: We terminated the trial principally because of severe ongoing side effects experienced by many of those receiving lithium, and with additional concerns about initial severe side effects (including psychosis) experienced by several assigned to lamotrigine. Analyses of study completer data for 28 participants suggested comparable efficacy of both medications; however, lamotrigine had a distinctly lower rate of severe side effects across the study. We calculated that if study trends on outcome measures were valid, then an extremely large sample would be required to demonstrate superiority of either drug, thus making it unlikely that any such adequately powered study will be mounted in the future. IMPLICATIONS/CONCLUSIONS: The small sample size limits any definitive conclusions, but our data suggest that lithium and lamotrigine are likely to have equal efficacy as mood stabilizers for those with a bipolar II condition but that, as maintenance treatments, lithium has more distinctive side effects.

The utility of daily mood ratings in clinical trials of patients with bipolar II disorder.

OBJECTIVE: To demonstrate that there can be distinctive differences in information generated by standard interval measures as against using daily monitoring for evaluating progress in those with a bipolar disorder. METHOD: We undertook a 20-week study of individuals with a bipolar II disorder randomly assigned to receive either lamotrigine or lithium. Patients were rated on standard measures of depression and hypomania at monthly intervals, and they also completed a daily rating measure of their mood swings. We sought to demonstrate the potential for differing interpretations that emerge from these measurement strategies. RESULTS: We graphed data for one subject who showed distinct improvement but demonstrated distinctly differing trajectories provided by monthly and daily data. In a second analysis, we considered sets of those who were judged as improving distinctly with lithium or lamotrigine to determine whether the drugs differed in speed of action, and again observed differing patterns between monthly and daily rating measures. CONCLUSIONS: A daily rating strategy appeared to provide additional and differing data compared to standard monthly measures. We therefore argue for the inclusion of daily mood ratings in clinical trials evaluating mood stabilisers and their use by clinicians in managing those with a bipolar II disorder.

Placebo response rates in trials of antidepressant drugs in adults with clinical depression: Increasing, decreasing, constant or all of the above?

OBJECTIVE: A seminal study quantified an increase in placebo (and drug) response rates in antidepressant trials during the eighties, with subsequent key systematic reviews reporting placebo response rates as either having continued to increase or stabilize in trial subjects with major depression. We therefore undertook an additional study examining a more recent period. METHOD: We analyze response rate data from 121 studies published over the 2001-2015 period and sourced from a previous meta-analysis of antidepressant drugs. RESULTS: Our analyses indicated trends for decreasing placebo response rates over the whole study period. Analyses of consolidated year blocks quantified a significant linear decrease and a significant cubic pattern in placebo response rates. Visual inspection of the yearly data patterns revealed wide fluctuations as well as distinct and correlated peaks and troughs for both placebo and drug responses. LIMITATIONS: The key studies we analyzed differed in a number of ways, including selection of inclusion criteria (especially in relation to analyzing published studies alone or together with unpublished studies) and analytic techniques. CONCLUSIONS: The markedly fluctuating placebo response patterns evidence an unstable 'signal' so leading principal studies to generate three mutually contradictory conclusions. We suggest that the increase in rates in the 1980s studies reflected the uptake and impact of 'major depression' being used as the diagnostic criterion, while the striking peaks and troughs observable over our study period argue for varying trial characteristics over time or rater biases in judging depression.

Mixed states in bipolar disorder: modelling, measuring and managing.

OBJECTIVE:: To consider whether consensus exists in recommendations for managing bipolar mixed states published in recent reviews and treatment guidelines, and to summarise what might be their best management. CONCLUSION:: Limitations to and changes in the definition of mixed states compromise diagnosis and management. The striking comparison between DSM-IV and DSM-5 criteria sets risks under-diagnosis and over-diagnosis. Current reviews and guidelines offer limited evidence to guide treatment; however, management should involve addressing the contribution of any antidepressant medication, and the introduction of a second-generation antipsychotic medication to stabilise the condition.

The Risk of Suicide and Self-Harm in Adolescents Is Influenced by the "Type" of Mood Disorder.

We sought to examine the extent to which suicidal ideation and self-harm are associated with a set of psychiatric conditions in senior high school students. A total of 1577 students completed an anonymous survey assessing lifetime rates of mood, anxiety, and eating disorders; the extent to which the presence of any depressive condition attracted bullying; help-seeking strategies; as well as rates of self-harm and suicidal ideation and plans over differing periods. Suicidal ideation and plans together with self-harm rates were distinctly higher in those with a melancholic depressive or a bipolar disorder (compared with those with nonmelancholic depression or an anxiety or eating disorder) and generally higher in females, whereas numbers of those with such conditions attending a mental health professional were low. Thus, for those with a mood disorder, the type of the condition appears to have a distinct impact on the likelihood of suicide and self-harm.

How well does a wellbeing measure predict psychiatric 'caseness' as well as suicide risk and self-harm in adolescents?

Screening for psychiatric disorders may be hampered by traditional measures that increase participant burden and elicit negative responses via denial and social desirability biases. This study examined the utility of a wellbeing measure to identify psychopathology and suicide risk in adolescent participants. 1,579 students from Sydney schools participated in a survey which assessed wellbeing using the Satisfaction With Life Scale (SWLS) as well as psychiatric disorders and suicide risk. Results showed that low scores on the SWLS discriminated adolescents who had experienced a psychiatric condition or suicidality from those not so assigned. Specifically, students with no psychiatric diagnosis yielded a mean SWLS score of 28.0 while for those assigned a diagnosis, mean scores ranged from 19.4-3.0 across the various psychiatric conditions. Students who reported any suicidal ideation yielded a mean SWLS score of 22.7, and those with a current suicidal plan yielded a mean score of 17.7. We derived SWLS cut-off scores for predicting psychiatric caseness and suicidality but established that they had low positive predictive power. The SWLS therefore appears to provide a limited proxy measure of the chance of a psychiatric disorder or psychological distress, and might usefully complement more direct measures of such states.

Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders.

OBJECTIVE: We sought to quantify the prevalence and differential prevalence of a bipolar disorder among family members of patients with a bipolar I or II disorder. METHODS: The sample comprised 1165 bipolar and 1041 unipolar patients, with the former then sub-typed as having either a bipolar I or II condition. Family history data was obtained via an online self-report tool. RESULTS: Prevalence of a family member having a bipolar disorder (of either sub-type) was distinctive (36.8%). Patients with a bipolar I disorder reported a slightly higher family history (41.2%) compared to patients with a bipolar II disorder (36.3%), and with both significantly higher than the rate of bipolar disorder in family members of unipolar depressed patients (18.5%). CONCLUSIONS: Findings support the view that bipolar disorder is heritable. The comparable rates in the two bipolar sub-types support the positioning of bipolar II disorder as a valid condition with strong genetic underpinnings.

The Pain Course: Exploring the Feasibility of an Internet-delivered Pain Management Program When Offered by a Tertiary Pain Management Service.

BACKGROUND: This study examined the acceptability and preliminary outcomes of an internet-delivered pain management program, the Pain Course, when offered by a specialist pain management clinic in a large public hospital. METHODS: A single-group feasibility open-trial design was used and 39 patients participated in the program, which ran for 8 weeks. Participants were supported through the program with weekly contact from a Clinical Psychologist at the clinic. RESULTS: All participants provided data at posttreatment and >90% of participants completed all 5 lessons of the course. High levels of satisfaction were observed and relatively little clinician time (M=71.99 min/participant; SD=32.82 min) was required to support patients through the program. Preliminary evidence of clinical improvements in depression symptoms (avg. improvement=38%; Cohen d=0.74), but not disability levels or anxiety symptoms, was observed in the overall sample. However, evidence of improvements was observed across all the primary outcomes among patients who had clinical levels of difficulties with disability (n=20; avg. improvement=11%; Cohen d=0.64), depression (n=17; avg. improvement=35%; Cohen d=1.24) and anxiety (n=8; avg. improvement=29%; Cohen d=0.57). CONCLUSIONS: These findings highlight the potential value of internet-delivered programs when provided by specialist pain management clinics as a part of their services and the value of larger scale studies in this area.