Bipolar Malaysian Guideline

1

2007

Malaysian Consensus Statement for the Treatment of

Bipolar Disorder

2 Malaysian Consensus Statement for the Treatment of Bipolar Disorder

Malaysian Consensus Statement for the Treatment of Bipolar Disorder 3

Foreword

I would like to congratulate all of those who contributed to the making of these guidelines. Bipolar disorder is diffi cult 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 HabilPresident 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 signifi cantly 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 ThambuChief EditorSenior Consultant PsychiatristHospital Universiti Kebangsaan Malaysia


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 Zafi dah 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.


Contents Page number

Introduction

Epidemiology

Defi nitions & 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

Specifi c 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

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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 diffi cult condition to diagnose, particularly if individuals are only evaluated during the depressive phase.3

• Bipolar disorder is associated with an increased incidence of co–morbidity 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


1.2 Epidemiology1,2

Prevalence Categories: Bipolar I, Bipolar II and Bipolar not otherwise specifi ed (NOS)

Bipolar symptoms experienced as part of cyclothymia, substanceinduced mood disorders, secondary to medical disorder and schizoaffective disorder-bipolar subtype General population incidence: Bipolar I - 0.5-2.4%; Bipolar II - 0.25.0%

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 diffi culty with work-related performance, leisure activities, and social and family interactions.

• Increase in lifetime health service utilization and need for welfare and disability benefi ts.

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


2.0 Defi nitions & 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

Early recognition 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

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

Bipolar I(F31.0-31.7)

Bipolar II(F31.8)

Bipolar NOS(F31.9)

Cyclothymia(F34.0)

Full manic or mixed episode

Obvious symptoms and functional impairment

Hypomania ≥4 days

Never a full manic episode

Recurrent major depression

Hypomania <4 days

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

Hypomaniaalternating with mild depression for ≥2 years


2.2 Features of Manic and Mixed Episodes1,19,20

Affective Cognitive Psychotic Physical

Pure Mania

Elevated, euphoric, or irritable mood

Expansive

Grandiose

Impulsive

Dysphoric/Mixed

Depression/anxiety

Irritability

Hostility or violence

Racing thoughts

Distractibility

Poor insight

Disorganization

Impaired attention

Impaired comprehension

Delusions

Hallucinations

Sensory hyperactivity

Rapid or pressured speech

Decreased need for sleep

Overly active, social, or hostile behavior

Increased libido

Recklessness, bizarre behavior, destruction of property

Sleep and endocrine abnormalities

2.3 Features of Bipolar Depression1,19,20

Affective Cognitive Physical

Sadness

Apathy

Anhedonia

Irritability

Anxiety

Hopelessness

Poor self-esteem

Poor concentration

Indecisiveness

Suicidal ideas

Self-blame

Change in sleep patterns

Change in appetite and/or weight

Decreased activity

Low energy

Slow thought and speech

Sleep and endocrine alterations


Acute Treatment of Mania

Sec

ond-

line

Less Severe Severe

No Response

Firs

t-lin

e

MonotherapyLithium or Sodium valproate or Atypical antipsychotic

Combination

Atypical antipsychotics recommended overtypical antipsychotics

CombinationLithium orSodium valproate AND

Atypical antipsychotic ORSwitch to carbamazepine

Lithium orSodium valproate ANDAtypical antipsychotic

3.1 Acute Treatment of Mania21-40

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.)


Acute Treatment of Bipolar Depression

Less Severe Severe

Seco

nd-li

neFi

rst-l

ine

MonotherapyLithium orLamotrigine orQuetiapine

CombinationSSRI + Olanzapine

Combination

Monotherapy with antidepressants is not recommended47

No Response

Combination

Change existing antidepressantCombination with Lamotrigine

Lithium or Lamotrigineor Quetiapine AND SSRI

3.2 Acute Treatment of Bipolar Depression41-46

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


Maintenance Therapy

Subthreshold symptoms or breakthrough mood episodes

Combination

ADD second maintenance medication

OR

atypical antipsychotic

OR

antidepressant

3.3 Maintenance Therapy21,49-51

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.


Rapid CyclingThe 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

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.


3.5 Specifi c 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 benefi t 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 therapyBehavioral 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 signifi cant improvement in family functioning, demonstrated fewer relapses, had longer survival intervals and reduced rates of hospitalization. 58,59

Group psychoeducationGroup 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 specifi cally designed for relapse prevention for patients who suffer from frequent relapses.

Consider family therapy for patients from families with high expressed emotion.


4.0 Appendix

4.1 Diagnostic Scales

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

Scale Sensitivity Specifi cityClinician-Administered Rating Scale for Mania(CARS-M)

0.85 0.87

Mini International Neuropsychiatric Inventory (MINI)

0.89 0.97

Psychosis Screening Questionnaire (PSQ) 0.96 0.95

Mood Disorder Questionnaire (MDQ) 0.72 0.90

Brief Psychiatric Rating Scale (BPRS) 0.67 0.72

Of the fi ve scales listed above, the three best validated for fi 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 diffi culties that make it diffi cult 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 confi rm 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 fi rst-degree relatives increases the likelihood of bipolar II disorder by 8–18 times compared to those with no family history.


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

◊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

––+Chlorpromazine†

––+◊Ziprasidone†

+–+^Quetiapine

–

–

+◊^

Risperidone† –+

+◊^

Olanzapine

–++◊Aripiprazole§

Antipsychotics

Carbamazepineextended-releasecapsules

–++Lithium

–+–Lamotrigine

––+Valproate

Mood Stabilizers

Depression*MaintenanceManiaAgents

+◊ ––

Drugs in order of approval


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Lithium carbonate

Lithium sulfate

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 doses400- g controlled-release tab: 400 mg-1.2 g PO once daily. Higher doses divided throughout the day may be needed450-mg tab: 450-900 mg PO bidMaintenance treatment:250-mg tab: 250-500 mg/day PO Adjust dose after 7 days based on serum levels300-mg cap or tab: 400 mg-1.2 g/day PO in divided doses400-mg controlled-release tab: 400 mg-1.2 g PO once daily450-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

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, hypermagnese- mia, 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

Carbamazepine 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 POUsual dose: 400-600 mg/day PO in divided dosesMax dose: 1600 mg/day

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

Lamotrigine Bipolar depression:Initial dose: 25 mg/day PO x 2 wk then increase by 25 mg increments every 2 wk Initial dose in patienttaking 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 Carbamaze-pine: 50 mg PO once daily x 2 wk then increase dose by 25-50 mg increments every 2 wkUsual dose: 200 mg/day POMax dose: 500 mg/day

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

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 responseorAdminister loading dose of 20 mg/kg/day PO in divided dosesUsual dose: 500-2000 mg/day PO in divided dosesMax dose: 3000 mg/dayNa Valproate slow-release film-coated tab:-Total daily dose is similar to regular-release tab- Dose may be administered once daily

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

ANTICONVULSANTS

4.3 Dosage Guidelines


4.3 Dosage Guidelines (Cont’d)

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ATYPICAL ANTIPSYCHOTICS

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Olanzapine

Quetiapine

Acute mania:10-15 mg PO once dailyMax dose: 20 mg/dayPrevention of recurrence of bipolar disorder: Start at 10 mg PO once daily

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.

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

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.

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

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.

Aripiprazole Acute mania:30 mg PO once dailyMay decrease to 15 mg PO once daily

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

Risperidone Acute mania*:Initial dose: 2-3 mg/day PO May increase dose if needed by 1mg/dayevery not more frequently than 24 hrUsual dose: 2-6 mg/dayMax dose: 10 mg/day

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

Notes:

* Not an approved indication in MalaysiaAdapted from MIMS Malaysia 2006/2007


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