Korean Medication Algorithm for Bipolar Disorder (KMAP-BP): Changes in Treatment Strategies for Bipolar Depression over 12 Years

Objective This study was conducted to examine how Canadian psychiatrists manage bipolar depression. Method A questionnaire specific to the treatment of bipolar depression was mailed to 1639 active members of the Canadian Psychiatric Association. Results Seven hundred and sixty-six completed questionnaires were returned (46.7%). Most psychiatrists indicated that a combination of psychotherapy and somatic therapy was their preferred approach. For bipolar disorder, depressed, lithium carbonate and selective serotonin reuptake inhibitors (SSRIs) were the preferred treatment strategies. For substitution, tricyclic antidepressants (TCAs) were the favoured choice. Lithium carbonate was the preferred choice for augmentation and addition. Conclusion These findings indicate that a combination of psychotherapy and somatic therapy is the preferred treatment approach for bipolar depression. Lithium carbonate and SSRIs are the favoured somatic therapies.

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Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

International Journal of Bipolar Disorders ◽

10.1186/s40345-019-0155-y ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

Maximilian Pilhatsch ◽

Thomas J Stamm ◽

Petra Stahl ◽

Ute Lewitzka ◽

Anne Berghöfer ◽

...

Keyword(s):

Bipolar Disorder ◽

Rating Scale ◽

Bipolar Depression ◽

Phenotypic Expression ◽

Anxiety Symptoms ◽

Controlled Study ◽

Double Blind ◽

Comorbid Anxiety ◽

Depressed Patients ◽

Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

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Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419826718 ◽

2019 ◽

Vol 53 (5) ◽

pp. 458-469 ◽

Cited By ~ 2

Author(s):

YC Janardhan Reddy ◽

Venugopal Jhanwar ◽

Rajesh Nagpal ◽

MS Reddy ◽

Nilesh Shah ◽

...

Keyword(s):

Bipolar Disorder ◽

Maintenance Treatment ◽

Bipolar Depression ◽

Mood Stabilizer ◽

Self Report ◽

Mood Stabilizers ◽

Prescribing Practices ◽

Term Outcome ◽

Cross Sectional ◽

Long Term Outcome

Objective: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. Method: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. Results: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. Limitations: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. Conclusion: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists’ practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

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Neural network dysfunction in bipolar depression: clues from the efficacy of lamotrigine

Biochemical Society Transactions ◽

10.1042/bst0371080 ◽

2009 ◽

Vol 37 (5) ◽

pp. 1080-1084 ◽

Cited By ~ 12

Author(s):

Charles H. Large ◽

Elena Di Daniel ◽

Xingbao Li ◽

Mark S. George

Keyword(s):

Bipolar Disorder ◽

Valproic Acid ◽

Protein Kinase ◽

Glycogen Synthase ◽

Bipolar Depression ◽

Inhibitory Effect ◽

Mood Stabilizers ◽

Mitogen Activated Protein Kinase ◽

Facilitatory Effect

One strategy to understand bipolar disorder is to study the mechanism of action of mood-stabilizing drugs, such as valproic acid and lithium. This approach has implicated a number of intracellular signalling elements, such as GSK3β (glycogen synthase kinase 3β), ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) or protein kinase C. However, lamotrigine does not seem to modulate any of these targets, which is intriguing given that its profile in the clinic differs from that of valproic acid or lithium, with greater efficacy to prevent episodes of depression than mania. The primary target of lamotrigine is the voltage-gated sodium channel, but it is unclear why inhibition of these channels might confer antidepressant efficacy. In healthy volunteers, we found that lamotrigine had a facilitatory effect on the BOLD (blood-oxygen-level-dependent) response to TMS (transcranial magnetic stimulation) of the prefrontal cortex. This effect was in contrast with an inhibitory effect of lamotrigine when TMS was applied over the motor cortex. In a follow-up study, a similar prefrontal specific facilitatory effect was observed in a larger cohort of healthy subjects, whereas valproic acid inhibited motor and prefrontal cortical TMS-induced BOLD response. In vitro, we found that lamotrigine (3–10 μM) enhanced the power of gamma frequency network oscillations induced by kainic acid in the rat hippocampus, an effect that was not observed with valproic acid (100 μM). These data suggest that lamotrigine has a positive effect on corticolimbic network function that may differentiate it from other mood stabilizers. The results are also consistent with the notion of corticolimbic network dysfunction in bipolar disorder.

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Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Psychological Medicine ◽

10.1017/s0033291714000804 ◽

2014 ◽

Vol 44 (16) ◽

pp. 3455-3467 ◽

Cited By ~ 17

Author(s):

A. Peters ◽

L. G. Sylvia ◽

P. V. da Silva Magalhães ◽

D. J. Miklowitz ◽

E. Frank ◽

...

Keyword(s):

Bipolar Disorder ◽

Collaborative Care ◽

Bipolar Depression ◽

Age At Onset ◽

Number Needed To Treat ◽

Systematic Treatment ◽

Illness Duration ◽

Bipolar Patients ◽

Depressive Episodes ◽

Intensive Psychotherapy

Background.The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.Method.Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.Results.Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.Conclusions.Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

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Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline

The British Journal of Psychiatry ◽

10.1192/bjp.bp.105.013045 ◽

2006 ◽

Vol 189 (2) ◽

pp. 124-131 ◽

Cited By ~ 186

Author(s):

R. M. Post ◽

L. L. Altshuler ◽

G. S. Leverich ◽

M. A. Frye ◽

W A. Nolen ◽

...

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Antidepressant Drugs ◽

Patient Treatment ◽

Adjunctive Treatment ◽

Prior History ◽

Rapid Cycling ◽

Acute Response ◽

Relative Risks ◽

Increased Risk

BackgroundFew studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression.AimsTo examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers.MethodIn a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers.ResultsA total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49–53%) and remission (34–41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline.ConclusionsMore caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.

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A clinical review of aripiprazole in bipolar depression and maintenance therapy of bipolar disorder

Yearbook of Psychiatry and Applied Mental Health ◽

10.1016/j.ypsy.2011.07.054 ◽

2012 ◽

Vol 2012 ◽

pp. 293-294

Author(s):

J.C. Ballenger

Keyword(s):

Bipolar Disorder ◽

Maintenance Therapy ◽

Clinical Review ◽

Bipolar Depression

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Genetic Variations Associated with Long-Term Treatment Response in Bipolar Depression

Genes ◽

10.3390/genes12081259 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1259

Author(s):

Gerard Anmella ◽

Silvia Vilches ◽

Jordi Espadaler ◽

Andrea Murru ◽

Isabella Pacchiarotti ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Bipolar Depression ◽

Scientific Evidence ◽

Term Treatment ◽

Response To Treatment ◽

Clinical Predictors ◽

Patient Response ◽

Long Term Treatment ◽

The Impact

Several pharmacogenetic-based decision support tools for psychoactive medication selection are available. However, the scientific evidence of the gene-drug pairs analyzed is mainly based on pharmacogenetic studies in patients with major depression or schizophrenia, and their clinical utility is mostly assessed in major depression. This study aimed at evaluating the impact of individual genes, with pharmacogenetic relevance in other psychiatric conditions, in the response to treatment in bipolar depression. Seventy-six patients diagnosed with bipolar disorder and an index major depressive episode were included in an observational retrospective study. Sociodemographic and clinical data were collected, and all patients were genotyped using a commercial multigene pharmacogenomic-based tool (Neuropharmagen®, AB-Biotics S.A., Barcelona, Spain). Multiple linear regression was used to identify pharmacogenetic and clinical predictors of efficacy and tolerability of medications. The pharmacogenetic variables response to serotonin-norepinephrine reuptake inhibitors (SNRIs) (ABCB1) and reduced metabolism of quetiapine (CYP3A4) predicted patient response to these medications, respectively. ABCB1 was also linked to the tolerability of SNRIs. An mTOR-related multigenic predictor was also associated with a lower number of adverse effects when including switch and autolytical ideation. Our results suggest that the predictors identified could be useful to guide the pharmacological treatment in bipolar disorder. Additional clinical studies are necessary to confirm these findings.

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Suicidality in patients with bipolar depression: findings from a lower middle-income country

BJPsych Open ◽

10.1192/bjo.2021.207 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S61-S61

Author(s):

Siqi Xue ◽

John Hodsoll ◽

Ameer Bukhsh Khoso ◽

Muhammad Omair Husain ◽

Imran B Chaudhry ◽

...

Keyword(s):

Bipolar Disorder ◽

Suicidal Ideation ◽

Rating Scale ◽

Bipolar Depression ◽

Demographic Data ◽

Middle Income Country ◽

Income Country ◽

Middle Income ◽

Biological Variables ◽

Lower Middle Income Country

AimsAmong low- and middle-income countries (LMICs), bipolar disorder is recognized as one of the leading causes of disease burden for adults and is associated with marked suicide risk. There are limited data on suicidal ideation in bipolar disorder from LMICs. This study presents cross-sectional data on the prevalence of suicidality and associated patient characteristics among patients with bipolar depression in Pakistan, a lower-middle income country and the fifth most populous country in the world.MethodParticipants were recruited through outpatient psychiatric clinics in between 2016–2019 in Karachi, Lahore, Hyderabad and Rawalpindi between 2016–2019. Participants were aged 18 to 65 years with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and proportional odds regression models were applied to establish correlates to suicidal ideation.ResultAmong the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88–0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16–1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40–0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03–1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. No patient demographic data, including age, gender, marital status, socioeconomic status, and years of education were associated with severity of suicidality.ConclusionThere exists a high prevalence of suicidal ideation among patients with bipolar depression in Pakistan. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression. More studies are needed to see whether such findings can be replicated in other similar LMIC settings, and to explore potential physiological pathways linking BMI, inflammatory biomarkers and suicidality in bipolar disorder.

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Psychotic symptoms in bipolar disorder: Two years’ retrospective study

Health Renaissance ◽

10.3126/hren.v13i1.17947 ◽

2017 ◽

Vol 13 (1) ◽

pp. 49-57

Author(s):

Baikuntha Raj Adhikari ◽

S Mishra ◽

S Nepal ◽

N Sapkota

Keyword(s):

Bipolar Disorder ◽

Retrospective Study ◽

Bipolar Depression ◽

Bipolar Disorders ◽

Unipolar Depression ◽

Common Type ◽

Psychotic Symptoms ◽

Mixed Episode ◽

Auditory Verbal Hallucinations ◽

Primary Substance

Background: Psychosis in bipolar disorder is common but still not well understood. There is paucity of literature from our country and none from this institute which serves the eastern part of Nepal.Objective: To describe the hallucinations and delusions in bipolar disorders in our place.Methods: Patients-record files of bipolar disorders with psychosis discharged in two years’ time from 2012 to 2014 were analysed. Patients with unipolar depression, recurrent depressive disorder, serious organic illness, and primary substance use disorders were excluded. Information was collected in a structured performa. Association of delusion and hallucination was observed.Results: During the study period, ninety-five patients with bipolardisorder had psychosis. Hallucination was present in 29 (30.5%) cases, and out of these 23 (79.3%) were cases of mania. In 26 (89.7%) patients, the hallucinations were mood congruent. The median duration of appearance of hallucination was 10 days and appeared early in mania. Among hallucinations, auditory verbal hallucinations were present in all 29 patients. Delusions were present in 77 (81.1%) of patients, and grandiose delusions were the most common. Grandiose delusions tended to occur even in the absence of hallucinations. Conclusion: Psychosis is common in bipolar disorder. Grandiose delusions are the most common delusion and are relatively independent of hallucination. The auditory verbal hallucinations are the most common type of hallucination. Hallucinations in mania tend to manifest earlier than in bipolar depression and mixed episode, and most of the hallucinations in bipolar disorder are mood congruent. Health Renaissance 2015;13 (1): 49-57

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