Malaysian Consensus Statement for the Treatment of

Bipolar Disorder

2007
1

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

Foreword
I would like to congratulate all of those who contributed to the making of these guidelines. Bipolar disorder is difcult to diagnose, especially if patients are seen only during the depressive phase. Drugs are available for treatment, but as clinicians it is essential that we manage our patients using evidence-based medicine. With a greater awareness of Bipolar II Disorder as part of the bipolar spectrum, a growing body of evidence will be available to aid clinicians in making treatment decisions for this disabling condition. By using these guidelines we will be able to standardize our local treatment approaches within an Asian context. Prof Dr Mohamad Hussain Habil President of Malaysian Psychiatric Association

Preface
Bipolar disorder, which was once thought to be neither common nor very serious, is now increasingly recognized as a major cause of disability and morbidity, and contributes signicantly to mortality among psychiatric patients. Part of the problem is late recognition and inadequate or even inappropriate treatment of this condition; for example, giving patients antidepressants alone which tend to destabilize mood. It is hoped that a guideline such as this will help doctors in the challenging task of patient management. I wish to congratulate the Young Psychiatrists Section of the Malaysian Psychiatric Association for their sterling efforts in producing this booklet. While it is not a CPG, nevertheless it was an arduous task. I hope they may continue to work as well as this in producing guidelines for other conditions. I also wish to thank the Editorial Advisory Group for their many suggestions, as well as acknowledge authors of previously produced guidelines which have helped in this process. Prof Dr Maniam Thambu Chief Editor Senior Consultant Psychiatrist Hospital Universiti Kebangsaan Malaysia

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

Honorary Editorial Advisory Board

Chief Editor: Prof Dr Maniam Thambu (Universiti Kebangsaan Malaysia) Co-Chief Editors: Prof Dr Stephen Jambunathan (Universiti Malaya Medical Centre) Dr Philip George (International Medical University) Editorial Board Committee: Prof Dr Mohamad Hussain Habil (Universiti Malaya Medical Centre) Dato Dr Suarn Singh Jasmit Singh (Hospital Bahagia) Dr Benjamin Chan Teck Ming (Hospital Permai) Dr Ahmad Hatim Sulaiman (Universiti Malaya Medical Centre) Dr Jesjeet Singh Gill Singh (Universiti Malaya Medical Centre) Dr Joseph Jacob (Universiti Malaya Medical Centre) Dr Siti Nor Aizah (Hospital Kuala Lumpur)

Young Psychiatrist Section Workshop*

Chairperson: Prof Dr Stephen Jambunathan (Universiti Malaya Medical Centre) Co-Chairperson: Dr Philip George (International Medical University) Members: Dr Parameswaran Ramasamy (Hospital Seremban) Dr Subash Kumar Pillai (Universiti Malaya Medical Centre) Dr Koh Ong Hui (Universiti Malaya Medical Centre) Dr Joseph Jacob (Universiti Malaya Medical Centre) Dr John Tan Jin Teong (Universiti Malaya Medical Centre) Dr Rusdi Abdul Rashid (Universiti Malaya Medical Centre) Dr Shamilla Kanagasundram (Universiti Malaya Medical Centre) Dr Nik Ruzyanei Nik Jaafar (Hospital Universiti Kebangsaan Malaysia) Dr Marhani Midin (Hospital Universiti Kebangsaan Malaysia) Dr Zarina Zainan Abidin (Hospital Universiti Sains Malaysia) Dr Norzila Zakaria (Hospital Universiti Sains Malaysia) Dr Asrenee Ab Razak (Hospital Universiti Sains Malaysia) Dr Rohayah Husain (Hospital Universiti Sains Malaysia) Dr Mohd Najib Mohd Alwi ((Hospital Universiti Sains Malaysia) Dr Norhalina Bahar (Hospital Kuala Lumpur) Dr Sharifah Suziah Syed Mokhtar (Hospital Kuala Lumpur) Dr Norliza Che Mi (Hospital Kuala Lumpur) Dr Uma Visvalingam (Hospital Kuala Lumpur) Dr Azhar Salleh (Universiti Pertanian Malaysia) Dr Omar Ali (Hospital Alor Setar) Dr Ahmad Syukri Chew Abdullah (Hospital Bahagia) Dr Ramli Mohd Ali (Hospital Selayang) Dr Umadevi Narayanan (Hospital Seremban) Dr Eizhwan Hamdie Yusoff (Hospital Tengku Ampuan Rahimah) Dr Chin Loi Fei (Hospital Permai) Dr Sivakumar Thurairajasingam (Monash University) Dr Norhashim Ahmad (Hospital Sultanah Aminah) Dr Wan Zadah Wan Nawawi (Hospital Sultanah Aminah) Dr Ibrahim Abu Samah (Hospital Pakar Sultanah Fatimah) Dr Nurulwafa Hussain (Hospital Melaka) Dr Fariza Yahya (Hospital Kota Bahru) Dr Ahmad Zabidin Zakaria (Hospital Kota Bahru) Dr Khairi Che Mat (Hospital Kota Bahru) Dr Siow Yuen Chin (Klinik Pakar Siow)
*Acknowlegement to the workshop members who participated in the discussion and review of the Malaysian Consensus Statement for the Treatment of Bipolar Disorder.

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

Contents

Page number

Introduction Epidemiology Denitions & diagnosis Diagnostic overview (DSM-IV and ICD-10) Features of manic and mixed episodes Features of bipolar depression Acute treatment of mania Acute Treatment of bipolar depression Maintenance therapy Rapid cycling Treatment in special populations Specic psychosocial interventions Cognitive behavioral therapy (CBT) Interpersonal and social rhythm therapy (IPSRT) Behavioral family therapy Group psychoeducation Appendix Diagnostic scales FDA- & DCA-approved treatment options Dosage guidelines References

6 7 8 8 9 9 10 11 12 13 13 14 14 14 14 14 15 15 16 17 19

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

This consensus statement provides general guidelines based on a review of the available evidence. However, treatment for each patient should be tailored according to the individual circumstances, guided by clinical judgment. This document is not legally binding.

1.1

Introduction
Bipolar disorder is relatively common with a lifetime prevalence of approximately 1.3%.1,2 It is a difcult condition to diagnose, particularly if individuals are only evaluated during the depressive phase.3 Bipolar disorder is associated with an increased incidence of comorbidity with substance abuse, anxiety disorders, and personality disorders. Axis I or Axis II co-morbidity may be associated with an earlier age at onset and a worse course of bipolar illness. The illness can interfere repeatedly and sometimes profoundly with patients well-being and productivity and can be associated with increased morbidity and mortality. Drugs are available for the treatment of individuals, but they require careful management with regular follow up. Compliance to treatment appears to be a major problem.4 Psychosocial interventions have also been introduced and evaluated, but need to be brought to more general attention. Clinical guidelines concentrating on expert review of the literature, clinical practice and critical appraisal of the primary evidence are required for effective diagnosis, treatment and management of this disorder.5-7

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

1.2 Epidemiology1,2
Prevalence
Categories: Bipolar I, Bipolar II and Bipolar not otherwise specied (NOS) Bipolar symptoms experienced as part of cyclothymia, substance induced mood disorders, secondary to medical disorder and schizoaffective disorder-bipolar subtype General population incidence: Bipolar I - 0.5-2.4%; Bipolar II - 0.2 5.0% Prevalence of Bipolar I equal between genders Subsyndromal manic symptoms have an incidence of 3.0-6.5% Almost 50% have co-morbid anxiety disorders and substance abuse True prevalence unknown lack of reliable diagnostic instruments

Age of onset

Mean age between 17 and 21 years; may have prior behavioral problems. Early onset disrupts education, career and social development. >10% of teenagers with recurrent depression develop bipolar disorder. First presentation of mania >60 years likely associated with organic illness.

Burden of illness

Disability and negative impact on quality-of-life: More difculty with work-related performance, leisure activities, and social and family interactions. Increase in lifetime health service utilization and need for welfare and disability benets.

Suicide risk

Lifetime risk: 17-19% (15-20x the general population) 20-50% of bipolar patients have at least one suicide attempt 4,8-14 Risk factors: 14-18 history of suicide attempt family history of suicidal behavior severity/number of depressive episodes alcohol/substance abuse level of pessimism level of aggression/impulsivity younger age of onset

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

2.0 Denitions & Diagnosis

Diagnosis
Gold Standard: Clinical diagnosis 2 main diagnostic schemes: ICD-1019 & DSM-IV1 Research tools: The Scheduled Clinical Interview for DSM (SCID) & present state examination (PSE)

Delay in diagnosis

May be associated with instability of illness Late occurrence of manic/hypomanic episodes Late presentation of illness Masked by recurrent depressive episodes Little/no evidence regarding: early/prodromal symptoms that allow predictions of illness recommendations on the use of screening tools impact of pre-symptomatic treatment on outcome

Early recognition

2.1 Diagnostic Overview (DSM-IV and ICD-10)

Bipolar I (F31.0-31.7)
Full manic or mixed episode

Bipolar II (F31.8)
Hypomania 4 days

Bipolar NOS (F31.9)

Hypomania <4 days

Cyclothymia (F34.0)
Hypomania alternating with mild depression for 2 years

Obvious symptoms and functional impairment

Never a full manic episode Recurrent major depression

Rapid mood alterations or mood episodes that do not meet criteria for any of the bipolar mood disorders

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

2.2 Features of Manic and Mixed Episodes1,19,20

Affective
Pure Mania Elevated, euphoric, or irritable mood

Cognitive
Racing thoughts Distractibility Poor insight Disorganization Impaired attention Impaired comprehension

Psychotic
Delusions Hallucinations Sensory hyperactivity

Physical
Rapid or pressured speech Decreased need for sleep Overly active, social, or hostile behavior Increased libido Recklessness, bizarre behavior, destruction of property

Expansive Grandiose

Impulsive

Dysphoric/Mixed Depression/anxiety Irritability Hostility or violence Sleep and endocrine abnormalities

2.3 Features of Bipolar Depression1,19,20

Affective
Sadness Apathy Anhedonia Irritability Anxiety Hopelessness

Cognitive
Poor self-esteem Poor concentration Indecisiveness Suicidal ideas Self-blame

Physical
Change in sleep patterns Change in appetite and/or weight Decreased activity Low energy Slow thought and speech Sleep and endocrine alterations

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

3.1

Acute Treatment of Mania21-40

Acute Treatment of Mania

First-line
Less Severe
Monotherapy
Lithium or Sodium valproate or Atypical antipsychotic

Severe
Combination
Lithium or Sodium valproate AND Atypical antipsychotic

Second-line

No Response
Combination
Lithium or Sodium valproate AND Atypical antipsychotic OR Switch to carbamazepine

Atypical antipsychotics recommended over typical antipsychotics

Notes: Consider ECT if symptoms are inadequately controlled or if mania is too severe. Consider clozapine for refractory illness (This is off-label use and must be indicated as such in patients notes. The usual precautions for the use of clozapine should be taken.)

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Malaysian Consensus Statement for the Treatment of Bipolar Disorder

3.2 Acute Treatment of Bipolar Depression41-46

Acute Treatment of Bipolar Depression

Less Severe
First-line

Severe Combination
Lithium or Lamotrigine or Quetiapine AND SSRI

Monotherapy
Lithium or Lamotrigine or Quetiapine

Combination
SSRI + Olanzapine

Second-line

No Response
Combination
Change existing antidepressant Combination with Lamotrigine

Monotherapy with antidepressants is not recommended47

Notes: Add ECT for patients with high suicidal risk, psychosis or severe depression during pregnancy or life-threatening situation. Both Lithium and lamotrigine are off-label use for acute treatment of bipolar depression, but recommended with substantial clinical evidence.41,48

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

11

3.3 Maintenance Therapy21,49-51

Maintenance Therapy
Subthreshold symptoms or breakthrough mood episodes

Combination ADD second maintenance medication OR atypical antipsychotic OR antidepressant

Notes: Consider clozapine in refractory patients (This is off-label use and must be indicated as such in patients notes. The usual precautions for the use of clozapine should be taken.) Maintenance ECT may be considered for patients who respond to ECT during an acute episode but do poorly on oral agents. The mood stabilizer chosen should be based on evidence that has been effective for the past episode.

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Malaysian Consensus Statement for the Treatment of Bipolar Disorder

The initial treatment for patients who experience rapid cycling can include valproate52 or quetiapine44,45 and may include lithium.53 An alternative treatment is lamotrigine.53 For many patients, combinations of medications are required.53

Rapid Cycling

3.4 Treatment in special populations

In the elderly, consider substantially lower doses of psychotropic medicines of all classes for all phases of treatment. In pregnancy, there is a risk of teratogenicity from the medications used in long-term treatment. Lowest risks appear to be associated with antipsychotics, lamotrigine, and antidepressants. Higher risks appear to be associated with lithium, carbamazepine, valproate.54,55 In lactation, data is sparse, but none of the medications used to treat bipolar disorder is a strict contraindication to breast feeding. Lithium is a relative contraindication. Generally, a high vigilance for adverse effects on the baby should be observed. Children and Adolescents: The diagnosis of childhood bipolar disorder remains challenging, in part because of high rates of co-morbidity with other common childhood disorders. Children with mania frequently present with atypical symptoms. A diagnosis of bipolar disorder should be considered for any youth with a marked deterioration in functioning associated with either mood or psychotic symptoms. Like adult bipolar disorder, childhood-onset bipolar disorder has a chronic course with a high rate of recurrence. Evidence suggests that prophylactic therapy is needed.

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

13

3.5 Specic Psychosocial Interventions

Psychosocial interventions include a variety of approaches such as peer support, cognitive behavioral therapy, family therapy, interpersonal therapy and patient education.

Cognitive behavioral therapy (CBT)

CBT is a treatment based on the assumption that thinking, mood and behavior affect one another. The aim is to teach patients techniques to monitor, examine and change the dysfunctional thinking and behavior associated with undesirable mood states. Compared to treatment as usual or a waiting list control, 7 to 25 sessions of CBT have benet for both relapse prevention and improved social functioning over follow-up periods of up to 18 months.56

Interpersonal and social rhythm therapy (IPSRT)

IPSRT teaches patients to regularize their sleep-wake patterns, work, exercise, meal times, and other daily activities in addition to therapy for interpersonal problem areas.57

Behavioral family therapy

Behavioral family therapy has three main components: psychoeducation, communication enhancement training, and problem-solving skills. This is designed to improve family functioning, improve mood, and reduce the risk of relapse. Members of families who received therapy showed signicant improvement in family functioning, demonstrated fewer relapses, had longer survival intervals and reduced rates of hospitalization. 58,59

Group psychoeducation

Group psychoeducation is focused on improving four main issues: Illness awareness Treatment compliance Early detection of prodromal symptoms and recurrences, and Lifestyle regularity Psychosocial interventions enhance care, can increase treatment adherence, and reduce the risk of relapse. Consider cognitive therapy specically designed for relapse prevention for patients who suffer from frequent relapses. Consider family therapy for patients from families with high expressed emotion.

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Malaysian Consensus Statement for the Treatment of Bipolar Disorder

4.0 Appendix 4.1 Diagnostic Scales

The absence of a gold standard distinct from clinical diagnosis makes it difcult to compare the accuracy of available scales with clinical assessment.

Scale
Clinician-Administered Rating Scale for Mania (CARS-M) Mini International Neuropsychiatric Inventory (MINI) Psychosis Screening Questionnaire (PSQ) Mood Disorder Questionnaire (MDQ) Brief Psychiatric Rating Scale (BPRS)

Sensitivity 0.85 0.89 0.96 0.72 0.67

Specicity 0.87 0.97 0.95 0.90 0.72

Of the ve scales listed above, the three best validated for rst admission bipolar patients are the PSQ, MDQ, and the BPRS. The Mood Disorder Questionnaire (MDQ) may be a useful screening instrument. Endorsement of two or more symptoms by an individual should alert the physician to further explore potential manic/hypomanic symptoms in more detail. Patients seldom recognize hypomania as a problem, particularly when being questioned in an acute depression, as they may have concentration and memory difculties that make it difcult to recall either hypomanic or even manic episodes. As such, several screening questions for both mania and hypomania should be asked, and if available, collateral history from family or friends should be obtained. In uncertain cases, prospective use of a mood diary can be very useful in identifying symptoms of a manic or hypomanic episodes. The best way to conrm the diagnosis may be to assess the patient on those days when the patient rates symptoms in the mood diary in the hypomanic/manic range. Screening for a family history of bipolar disorder is critical. A positive family history among rst-degree relatives increases the likelihood of bipolar II disorder by 818 times compared to those with no family history.
Malaysian Consensus Statement for the Treatment of Bipolar Disorder

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4.2 FDA- & DCA-Approved Treatment Options in Bipolar I Disorder

Agents
Mood Stabilizers Lithium Valproate Lamotrigine Carbamazepine extended-release capsules Antipsychotics Chlorpromazine Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole

Mania

Maintenance

Depression*

+ + +

+ +

+ +^

+ +

+^ +^ + +

Drugs in order of approval

Mixed episodes ^Combination with lithium/valproate *Depression associated with bipolar I disorder Not DCA approved for mania Aripiprazole not DCA approved for maintenance

FDA = US Food and Drug Administration. DCA = Malaysia Drug Control Authority

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Malaysian Consensus Statement for the Treatment of Bipolar Disorder

4.3 Dosage Guidelines

ANTICONVULSANTS Drug
Lithium carbonate

Dosage
Acute mania: 250-mg tab: 1-1.5 g/day PO in divided doses 300-mg cap or tab: 1.5-2 g/day PO in divided doses 400- g controlled-release tab: 400 mg1.2 g PO once daily. Higher doses divided throughout the day may be needed 450-mg tab: 450-900 mg PO bid Maintenance treatment: 250-mg tab: 250-500 mg/day PO Adjust dose after 7 days based on serum levels 300-mg cap or tab: 400 mg-1.2 g/day PO in divided doses 400-mg controlled-release tab: 400 mg1.2 g PO once daily 450-mg tab: 450 mg PO bid Acute mania: 660-mg sustained-release tab: 330 mg PO x 2 days then, 330 mg PO bid x 2 days, then 990 mg PO once daily x 2 days, then 1320 mg/day PO

Remarks
Adverse Reactions Initial effects which may abate w/ continued treatment: N/V, diarrhea, vertigo, muscle weakness, dazed feeling. Tremor, polyuria, polydipsia may persist Wt gain, edema (should be treated w/ diuretics), hypercalcemia, hypermagnesemia, hyperparathyroidism, acne, psoriasis, rashes, benign leucocytosis, ECG changes Long-term side effects: Hypothyroidism, goiter, rarely hyperthyroidism, mild memory or cognitive impairment, renal function & histologic changes Toxic effects may occur at serum levels >1.5 mmol/L & may occur at lower levels - Toxicity: Diarrhea, vomiting, anorexia, muscle weakness, lethargy, ataxia, giddiness, blurred vision, coarse tremor, lack of coordination, etc Special Instructions Preparations vary widely in bioavailability Narrow therapeutic range Start in low divided doses to minimize side effects & titrate upward to desired serum conc, desired response & min side effects The initial dose given is adjusted after 4-7 days according to the serum Lithium level. Steady state conc levels are usually reached 5 days after dose adjustment (Sample should be taken 12 hr after preceding dose) Suggest check serum conc wkly until dosage has remained constant x 4 wk. Then monitor serum conc every 3 mth Serum levels should be checked if with change in Lithium preparation, medical illness, manic or depressive episode, pregnancy, change in concomitant medication administration, signs of toxicity Acute mania serum level: 0.6-1 mmol/L Maintenance serum level: 0.4-0.8 mmol/L Pretreatment & periodic routine clinical monitoring is necessary: Renal function, urine analysis, thyroid function, cardiac function esp in those w/ CV disease Instruct patients to maintain usual salt & fluid intake Adverse Reactions GI disturbances esp at start of therapy; may be decreased w/ administration w/ meals or enteric-coated forms & starting at lower doses Increased appetite, wt gain. Less common reactions include edema, headache, increased bleeding time, thrombocytopenia, leucopenia, bone marrow depression, ataxia, tremor, sedation, confusion, rarely encephalopathy & coma Occasionally rashes. Rarely hirsutism, acne, Stevens-Johnson or erythema multiforme. Liver dysfunction including hepatic failure has occurred

Lithium sulfate

Valproate (Na Valproate)

Na Valproate regular release: Acute mania: 600-750 mg/day PO in divided doses. Increase dose by 200-500 mg/day at 3 day intervals until desired response or Administer loading dose of 20 mg/kg/day PO in divided doses Usual dose: 500-2000 mg/day PO in divided doses Max dose: 3000 mg/day Na Valproate slow-release film-coated tab: -Total daily dose is similar to regular-release tab - Dose may be administered once daily Bipolar depression: Initial dose: 25 mg/day PO x 2 wk then increase by 25 mg increments every 2 wk Initial dose in patient taking Divalproex: 25 mg PO every other day x 2 wk then increase dose by 25 mg increments every 2 wk Initial dose in patient taking Carbamazepine: 50 mg PO once daily x 2 wk then increase dose by 25-50 mg increments every 2 wk Usual dose: 200 mg/day PO Max dose: 500 mg/day Acute mania: Initial dose: 200-600 mg/day PO in divided doses May increase dose by 200 mg increments every 2-4 days (may increase up to 800-1000 mg/day, if patient is hospitalized) Dose range: 400-1600 mg/day PO Usual dose: 400-600 mg/day PO in divided doses Max dose: 1600 mg/day

Lamotrigine

Adverse Reactions Skin rashes, including Stevens-Johnson syndrome & toxic epidermal necrosis. Usually occur w/in 8 wk of starting therapy Other hypersensitivity symptoms: Fever, malaise, flu-like symptoms, drowsiness, lymphadenopathy, facial edema, rarely hepatic dysfunction Photosensitivity, angioedema, blurred vision, dizziness, drowsiness, insomnia, headache, N/V, etc

Carbamazepine

Adverse Reactions May decrease side effects by starting at low dose & increasing slowly Dizziness, drowsiness, ataxia, GI symptoms (eg dry mouth, abdominal pain, N/V, diarrhea, anorexia, constipation), rash which may be severe (eg Stevens-Johnson syndrome), photosensitivity reactions, systemic lupus erythematosus (SLE) Agranulocytosis, eosinophilia, aplastic anemia, leucopenia, leucocytosis, thrombocytopenia, & purpura, abnormalities of kidney & liver function, splenomegaly, lymphadenopathy, hyponatremia, edema, paresthesia, headache, arrhythmias, heart block, heart failure, etc

Malaysian Consensus Statement for the Treatment of Bipolar Disorder

17

4.3 Dosage Guidelines (Contd)

ATYPICAL ANTIPSYCHOTICS Drug
Risperidone

Dosage
Acute mania*: Initial dose: 2-3 mg/day PO May increase dose if needed by 1mg/dayevery not more frequently than 24 hr Usual dose: 2-6 mg/day Max dose: 10 mg/day

Remarks
Adverse Reactions Insomnia, headache, anxiety, agitation, hypotension, orthostatic hypotension, tachycardia, sedation, dizziness, restlessness, extrapyramidal reactions (usually dose-dependent), dystonic reactions, pseudo-parkinsonism, neuroleptic malignant syndrome, tardive dyskinesia, altered central temp regulation, rash, rarely photosensitivity, sexual dysfunction, amenorrhea, GI upset, constipation, abdominal pain, wt gain Adverse Reactions Headache, insomnia, somnolence, nervousness, dizziness, hostility, agitation, postural hypotension, peripheral edema, tachycardia, hypotension, Parkinsonian events, dystonic reactions, amnesia, euphoria, anxiety, rash, abdominal pain, wt gain, increased appetite, hypertonia, tremor, arthralgia, rarely tardive dyskinesia. Uncommon abnormalities of glucose hemostasis Adverse Reactions Somnolence, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension, and dyspepsia. As with other antipsychotics, syncope, neuroleptic malignant syndrome, leucopenia, neutropenia and peripheral edema, have been associated with quetiapine.

Olanzapine

Acute mania: 10-15 mg PO once daily Max dose: 20 mg/day Prevention of recurrence of bipolar disorder: Start at 10 mg PO once daily

Quetiapine

Acute mania: As monotherapy or as adjunct therapy to mood stabilizers (lithium or divalproex), bd dosing: 1st 4 days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4). Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of not > 200 mg/day. Adjust dose within the range of 200-800 mg/day depending on clinical response and tolerability of the patient. Usual effective dose range: 400-800 mg/day. Depressive episodes associated with bipolar disorder: Once daily at bedtime, titrated from: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4), 400 mg (Day 5) and up to 600 mg by Day 8. Usual effective dose range: 300-600 mg. Elderly & patients with renal or hepatic impairment: Initial dose: 25 mg/day, increased daily, in increments of 25-50 mg, to an effective dose. Acute mania: 30 mg PO once daily May decrease to 15 mg PO once daily

Aripiprazole

Adverse Reactions Headache, GI effects (constipation, N/V), CNS effects (insomnia, anxiety, lightheadedness, drowsiness, tremor) somnolence may increase w/ higher dose; wt gain; CNS effects (tachycardia, orthostatic hypotension) Incidence of EPS is low w/ akathisia as most commonly reported; tardive dyskinesia is infrequent Special instructions Use w/ caution in patients w/ DM, known CV disease, cerebrovascular disease or diseases that would predispose patients to hypotension, patients w/ a history of seizure Adverse Reactions Insomnia, somnolence, asthenia, headache, constipation, dry mouth, NV, agitation, akathisia, dizziness, dystonia, EPS reactions, hypertonia, hyptension, postural hypotension, dyspepsia, increased LFTs, rash, choreoathetosis, depression, seizure, tardive dyskinesia, increase in prolactin levels Prolongation of QT interval Special Instructions Take w/ food Avoid in patients w/ known history of QT prolongation, recent MI or decompensated heart failure; use w/ caution in patients w/ bradycardia, cerebrovascular disease, significant CV illness, history of seizures, pituitary tumors, renal or hepatic impairment and predisposed to hypotension. Monitor serum K and Mg prior to treatment in patients at risk for significant electrolyte disturbances esp. hypokalemia Patient should be instructed to report symptoms of trosade de pointes (eg dizziness, palpitations or syncope) immediately to physician

Ziprasidone

Acute mania*: Initial dose: 40 mg PO bid May increase to 60 or 80 mg PO bid on the 2nd day of therapy. Adjust dose based on desired effect and tolerability.

Notes: * Not an approved indication in Malaysia Adapted from MIMS Malaysia 2006/2007

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Malaysian Consensus Statement for the Treatment of Bipolar Disorder

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