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Is increased libido an atypical symptom of bipolar depression? An interesting case

Mahadevan R, Nik Jaafar NR, Sidi H, Midin M, Das S

J Sex Med, 2013 Mar;10(3):883-6.
PMID: 23036068 DOI: 10.1111/j.1743-6109.2012.02949.x

Decreased libido is recognized as one of the vegetative symptoms of depression. Increased libido has not been acknowledged as one of its symptoms, neither has it been reported, particularly in depressed bipolar patients.

Matched MeSH terms: Bipolar Disorder/drug therapy
The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness

Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al.

J Clin Psychiatry, 2009;70 Suppl 4:1-46; quiz 47-8.
PMID: 19686636

OBJECTIVES: Poor adherence to medication treatment can have devastating consequences for patients with mental illness. The goal of this project was to develop recommendations for addressing adherence problems to improve patient outcomes.
METHODS: The editors identified important topics and questions concerning medication adherence problems in serious mental illness that are not fully addressed in the literature. A survey was developed containing 39 questions (521 options) asking about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. Results of the literature review and survey were used to develop recommendations for assessing and improving adherence in patients with serious mental illness.
RESULTS: ASSESSING ADHERENCE: The experts endorsed percentage of medication not taken as the preferred method of defining adherence, with 80% or more of medication taken endorsed as an appropriate cut-off for adherence in bipolar disorder and schizophrenia. Although self- and physician report are the most common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. The experts recommend that, if possible, clinicians also use more objective measures (e.g., pill counts, pharmacy records, and, when appropriate, serum levels such as are used for lithium). Use of a validated self-report scale may help improve accuracy.
SCOPE OF THE PROBLEM: The majority of the experts believed the average patient with schizophrenia or bipolar disorder in their practices takes only 51%-70% of prescribed medication. FACTORS ASSOCIATED WITH NONADHERENCE: The experts endorsed poor insight and lack of illness awareness, distress associated with specific side effects or a general fear of side effects, inadequate efficacy with persistent symptoms, and believing medications are no longer needed as the most important factors leading to adherence problems in schizophrenia and bipolar disorder. The experts considered weight gain a side effect that is very likely to lead to adherence problems in patients with schizophrenia and bipolar disorder; sedation was considered a more important contributor to adherence problems in bipolar disorder than schizophrenia. The experts rated persistent positive or negative symptoms in schizophrenia and persistent grandiosity and manic symptoms in bipolar disorder as the most important symptomatic contributors to adherence problems in these illnesses.
INTERVENTIONS: It is important to identify the specific factors that may be contributing to a patient's adherence problems in order to customize interventions to target those problems. Multiple problems may be involved, requiring a combination of interventions.
CONCLUSIONS: Adherence problems are complex and multidetermined. The experts recommended customized interventions focused on the underlying causes.

Matched MeSH terms: Bipolar Disorder/drug therapy
Fulltext Lithium neurotoxicity

Suraya Y, Yoong KY

Med J Malaysia, 2001 Sep;56(3):378-81.
PMID: 11732087

Inspite of the advent of newer antimanic drugs, lithium carbonate remains widely used in the treatment and prevention of manic-depressive illness. However care has to be exercised due to its low therapeutic index. The central nervous system and renal system are predominantly affected in acute lithium intoxication and is potentially lethal. The more common side effect involves the central nervous system. It occurs early and is preventable. We describe three cases of lithium toxicity admitted to Johor Bahru Hospital, with emphasis on its neurological preponderance.

Matched MeSH terms: Bipolar Disorder/drug therapy
Fulltext Long term lithium therapy in Malaysia

Ngen CC, Cheong IK

Med J Malaysia, 1989 Sep;44(3):199-203.
PMID: 2626134

Ten patients on long term lithium therapy (mean four years, range 1-10.5 years) were subjected to various renal, thyroid, haematological, cardiac and endocrine tests. There was impaired urinary concentrating ability in seven subjects, which was not responsive to vasopressin stimulation, suggesting a partial nephrogenic diabetes insipidus. Nine subjects had metabolic acidosis with higher urinary pH than expected suggesting presence of acidification defect in the kidney. No significant change in renal function, thyroid function, ECG or haematological parameters were detected. Our findings concur with previous reports from the West regarding the safety of lithium administration.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior

Chan LF, Eu CL, Soh SY, Maniam T, Shahidii Kadir Z, Chong BTW, et al.

J Psychiatr Pract, 2018 07;24(4):279-291.
PMID: 30427812 DOI: 10.1097/PRA.0000000000000316

Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Fulltext Executive function and attention span in euthymic patients with bipolar 1 disorder

Normala I, Abdul HA, Azlin B, Nik Ruzyanei NJ, Hazli Z, Shah SA

Med J Malaysia, 2010 Sep;65(3):199-203.
PMID: 21939168

This is a cross sectional comparison study to assess executive function and attention span in euthymic patients with bipolar 1 disorder. It compares the performance of these two cognitive domains in 40 patients with bipolar 1 disorder to that of 40 healthy normal subjects using Trail Making (TMT), Digit Span (Forward and Backward) and Verbal Fluency (VF) tests. The association between demographic, clinical characteristics and performance in all tests were examined. Patients with bipolar illness showed significant impairment with moderate to large effect sizes (VF = 0.67, TMT A = 0.52, TMT B = 0.81, Digit Forward = 0.97, Digit backward = 1.10) in all tasks of executive and attention functioning. These impairments are observed in the absence of active mood symptoms while duration and severity of illness are not found to have an effect on both cognitive domains. Medications received by patients with bipolar disorder have significant association with performance on executive tasks. The results of this study add on to the existing global evidence of cognitive impairment in bipolar illness despite its cross cultural differences. Its presence in the absence of mania, depression or mixed episode indicates that cognitive impairment is stable even after symptoms recovery.

Matched MeSH terms: Bipolar Disorder/drug therapy
Safety and efficacy of rapid dose administration of quetiapine in bipolar mania

Hatim A, Habil H, Jesjeet SG, Low CC, Joseph J, Jambunathan ST, et al.

Hum Psychopharmacol, 2006 Jul;21(5):313-8.
PMID: 16856220

In this open-label pilot study, 20 adult patients hospitalized for acute bipolar mania received oral quetiapine as a single evening dose of 200 mg on day 1, increased by 200 mg/day on days 2, 3, and 4 until 800 mg/day taken in 2 divided doses on day 4. From day 5 onward, patients received a flexible total dose of 400-800 mg/day until completion of 3 weeks of treatment. Safety and tolerability were assessed by adverse-event (AE)-related dropouts in week 1, incidence of AEs including EPS, changes in electrocardiogram, and vital signs. Efficacy was assessed using the YMRS, PANSS, and CGI scales. Nineteen of 20 patients (95%) completed the quetiapine rapid titration during week 1. Significant improvement was observed in YMRS, PANSS, and CGI Severity of Illness scores by day 5, and was maintained throughout the study. A reduction of > or = 50% in YMRS score was achieved by 75% of patients by day 7, and maintained to day 21. Overall, 20% of patients discontinued due to AEs. Agitation was the most common cause of AE-related study discontinuation. Thirty-five per cent of patients required dose adjustment due to AEs after rapid dose administration was completed. Most patients tolerated rapid titration of quetiapine to 800 mg/day by day 4 of therapy, with a significant improvement in manic symptoms by day 7 of treatment.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Factors Associated With Antidepressant Dosing in Asia: Findings From the Research on Asian Psychotropic Prescription Study

Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.

J Clin Psychopharmacol, 2016 Dec;36(6):716-719.
PMID: 27753726

In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Fulltext Branch retinal vein occlusion associated with quetiapine fumarate

Yong KC, Kah TA, Ghee YT, Siang LC, Bastion ML

BMC Ophthalmol, 2011;11:24.
PMID: 21867521 DOI: 10.1186/1471-2415-11-24

To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate.

Matched MeSH terms: Bipolar Disorder/drug therapy
Paradoxical pinpoint pupils with asenapine

Gill JS, Jambunathan S, Wong S, Wong A

Asia Pac Psychiatry, 2015 Jun;7(2):230.
PMID: 25923587 DOI: 10.1111/appy.12171
Matched MeSH terms: Bipolar Disorder/drug therapy*
Clinical evaluation and serum concentration of zuclopenthixol acetate in psychotic Asian patients: a single-dose preliminary study

Tan CH, Low BL, Ng LL, Khoo YM, Lee HS

Ther Drug Monit, 1993 Apr;15(2):108-12.
PMID: 8099240

Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer trans(E)-clopenthixol were determined by high-performance liquid chromatography after intramuscular injection. All patients improved, with the BPRS being significantly reduced (p < 0.001) at 72 h after injection. Adverse effects were generally few. The mean +/- SEM serum zuclopenthixol concentrations at 24, 48, and 72 h were 19.9 +/- 2.8, 31.5 +/- 4.5, and 17.8 +/- 2.9 micrograms/L, respectively. trans(E)-Clopenthixol concentrations ranged from negligible to 39.5 micrograms/L. This study confirms that a single intramuscular injection of 50 mg is adequate for managing severely disturbed psychotic patients for the first 3 days. The serum zuclopenthixol concentrations attained in the Asian patients were higher than those reported in Caucasian psychiatric patients. In some patients, a considerable amount of zuclopenthixol had been transformed to trans(E)-clopenthixol.

Matched MeSH terms: Bipolar Disorder/drug therapy
Fulltext Hypertensive bipolar: chronic lithium toxicity in patients taking ACE inhibitor

Masiran R, Abdul Aziz MF

BMJ Case Rep, 2017 Aug 28;2017.
PMID: 28847993 DOI: 10.1136/bcr-2017-220631

A patient with bipolar I disorder has been treated with lithium and haloperidol for the last 20 years and received an ACE inhibitor for his hypertension since 9 years ago. Despite regular clinic follow-ups and blood monitoring, he recently developed tremors and delirium. On hospital admission, serum level of lithium was far above toxic level. Mental state examination revealed an anxious and disorientated man with irrelevant speech. Immediate discontinuation of lithium resulted in slow reduction of serum lithium levels and gradual resolution of tremor but his delirium persisted for 2 weeks. His condition took a turn for the worse when he developed acute renal failure and arm abscess. We discussed about lithium toxicity and the vulnerability factors which have induced delirium and renal failure in this patient.

Matched MeSH terms: Bipolar Disorder/drug therapy
Fulltext Peripheral PDLIM5 expression in bipolar disorder and the effect of olanzapine administration

Zain MA, Jahan SN, Reynolds GP, Zainal NZ, Kanagasundram S, Mohamed Z

BMC Med Genet, 2012;13:91.
PMID: 23031404 DOI: 10.1186/1471-2350-13-91

One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on PDLIM5 mRNA expression in the peripheral blood leukocytes of BPD patients.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Melatonin in mood disorders

Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, et al.

World J. Biol. Psychiatry, 2006;7(3):138-51.
PMID: 16861139

The cyclic nature of depressive illness, the diurnal variations in its symptomatology and the existence of disturbed sleep-wake and core body temperature rhythms, all suggest that dysfunction of the circadian time keeping system may underlie the pathophysiology of depression. As a rhythm-regulating factor, the study of melatonin in various depressive illnesses has gained attention. Melatonin can be both a 'state marker' and a 'trait marker' of mood disorders. Measurement of melatonin either in saliva or plasma, or of its main metabolite 6-sulfatoxymelatonin in urine, have documented significant alterations in melatonin secretion in depressive patients during the acute phase of illness. Not only the levels but also the timing of melatonin secretion is altered in bipolar affective disorder and in patients with seasonal affective disorder (SAD). A phase delay of melatonin secretion takes place in SAD, as well as changes in the onset, duration and offset of melatonin secretion. Bright light treatment, that suppresses melatonin production, is effective in treating bipolar affective disorder and SAD, winter type. This review discusses the role of melatonin in the pathophysiology of bipolar disorder and SAD.

Matched MeSH terms: Bipolar Disorder/drug therapy
Fulltext Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression

Kato T, Ishigooka J, Miyajima M, Watabe K, Fujimori T, Masuda T, et al.

Psychiatry Clin Neurosci, 2020 Dec;74(12):635-644.
PMID: 32827348 DOI: 10.1111/pcn.13137

AIM: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan.
METHODS: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS).
RESULTS: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control.
CONCLUSION: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

Matched MeSH terms: Bipolar Disorder/drug therapy*
Clinical use of mood stabilizers with antidepressants in Asia: Report from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Projects in 2004 and 2013

Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.

J Clin Psychopharmacol, 2017 Apr;37(2):255-259.
PMID: 28146001 DOI: 10.1097/JCP.0000000000000670

OBJECTIVE: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries.
METHODS: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling.
RESULTS: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose.

CONCLUSIONS: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

Matched MeSH terms: Bipolar Disorder/drug therapy*

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