5. BIPOLAR DISORDER.pptx

Drugs for Bipolar Disorder Antimanic & Mood Stabilizing Drugs Learning Objectives • Describe Bipolar Disorder • Signs and Symptoms • Types and drugs used for treatment Classify drugs used in Bipolar Disorder and explain their: – MOA – Uses – Adverse effects – Drug interactions and precautions Bi...

Drugs for Bipolar Disorder Antimanic & Mood Stabilizing Drugs Learning Objectives • Describe Bipolar Disorder • Signs and Symptoms • Types and drugs used for treatment Classify drugs used in Bipolar Disorder and explain their: – MOA – Uses – Adverse effects – Drug interactions and precautions Bipolar Disorder • It’s a brain disorder that causes shifts in mood, energy, activity levels, ability to carry out day to day task, and behavior form the highs of mania on one extreme, to the lows of depression on the other. • Bipolar disorder is characterized by one or more episodes of mania or major depressive episodes • Mood episodes can be manic, depressed, or mixed. • They can be separated by periods of long stability or cycle rapidly. • They occur with or without psychosis. • Disability and other consequences (eg, increased risk of suicide) can be devastating to patients and families. • Correct and early diagnosis and treatment are essential to prevent complications and maximize response to treatment Signs and Symptoms Signs and Symptoms (Mania Episode) • Mood changes-feeling high (overly happy) • Irritable mood-agitation, feeling jumpy or weird • Behavior Change- talking fast, race of thoughts easily distracted, little sleep Sign and Symptoms (Depressive Episode) • Mood changes- feeling worried or empty • Loss of interest • Behavior change-tired, problems concentrating, irritable, changing of habits, thinking of death and suicide Classification of Drugs Classical agents • Lithium Newer agents • • • • • Aripiprazole Lusaridone Asenapine Olanzepine Carbamazepine Valproate Clonazepam Ziprasidone Iloperidone Queitapine Haloperidol Others Lithium • Lithium is effective in treatment of the manic phase of bipolar disorder • Continues to be used for acute-phase illness and for prevention of recurrent manic and depressive episodes. • Lithium is established as the standard antimanic and mood stabilizing drug. • Its also prescribed for Major Depressive Disorder • Over the past 2 decades, several anticonvulsants and atypical antipsychotics have emerged as alternatives to lithium with comparable efficacy. Pharmacokinetics of Lithium Absorption: Rapid and complete from the gut Distribution: Through out the body water Half-life : 20 h. Elimination: Kidneys at a rate one fifth that of creatinine. Plasma levels should be monitored, especially during the first weeks of therapy, to establish an effective and safe dosage regimen. For acute symptoms, the target therapeutic plasma concentration is 0.8– 1.2 mEq/L and for maintenance 0.4–0.7 mEq/L. Dehydration, or treatment with thiazides, NSAIDs, ACEIs, and loop diuretics, may result in an increase of lithium in the blood to toxic levels. Caffeine and theophylline increase the renal clearance of lithium. Mechanism of Action • The drug inhibits several enzymes involved in the recycling of neuronal membrane phosphoinositides. • This action may result in depletion of the second-messenger source, phosphatidylinositol bisphosphate (PIP2), which, in turn, would decrease generation of inositol trisphosphate (IP3) and diacylglycerol (DAG). • These second messengers are important in amine neurotransmission, including that mediated by central adrenoceptors and muscarinic receptors. • Inhibition of glycogen synthase kinase-3 (GSK3) is another important result and inhibition of β-catenin, a messenger involved in insulin-like growth factor and brain-derived neurotrophic factor (BDNF) has been implicated. Side effects • Common SE but are mostly tolerable. • Toxicity occurs at levels only marginally higher than therapeutic levels. 1. Nausea, vomiting and mild diarrhoea occur initially, can be minimized by starting at lower doses. 2. Thirst and polyuria are experienced by most, some fluid retention may occur initially, but clears later. 3. Fine tremors are noted even at therapeutic concentrations. 4. CNS toxicity manifests as plasma concentration rises producing coarse tremors, giddiness, ataxia, motor incoordination, nystagmus, mental confusion, slurred speech, hyper-reflexia Clinical Use • Lithium carbonate continues to be used for the treatment of bipolar disorder (manic-depressive disease) although other drugs including some anticonvulsants and second-generation antipsychotics are equally effective. • Maintenance therapy with lithium decreases manic behavior and reduces both the frequency and the magnitude of mood swings. • Antipsychotic agents and/or benzodiazepines are commonly required at the initiation of treatment because both lithium and valproate have a slow onset of action. • Olanzapine, quetiapine, cariprazine, asenapine, aripiprazole, risperidone, and ziprasidone are also approved for acute mania. • Although lithium has protective effects against suicide and self-harm, antidepressant drugs are often used concurrently during maintenance. Note that monotherapy with antidepressants can precipitate mania in bipolar patients. • Lithium - Prevention of both manic and depressive episodes • Aggressive behavior • Borderline personality disorder • Bulimia nervosa • Cluster headaches Drugs classification and its mechanism Drug Class Mechanism Lithium Mood stabilizer Aripiprazole Atypical antipsychotic Asenapine Atypical antipsychotic Cariprazine Atypical antipsychotic Lurasidone Atypical antipsychotic Olanzapine Quetiapine Atypical antipsychotic Atypical antipsychotic Ziprasidone Atypical antipsychotic Valproate Anticonvulsant Inhibits several enzymes involved in the recycling of neuronal membrane phosphoinositides 5-HT2-receptor blockade 5-HT2-receptor blockade with some D2 blockade 5-HT2-receptor blockade 5-HT2-receptor blockade with some D2 blockade 5-HT2-receptor blockade and D4 5-HT2-receptor blockade and multi transmitter targets 5-HT2-receptor blockade with some D2 blockade Prolongs inactivation of voltage gated sodium channels, agonist activity at VALPROATE and CARBAMAZEPINE • These are known anticonvulsant agents acts by prolonging inactivation of voltage gated sodium channels • Used along with lithium to help the pharmacological action • Valproate is now a first line treatment of acute mania in which high dose valproate acts faster than lithium and is an alternative to antipsychotic ± benzodiazepine. • To patients: Not responding or resistant to lithium • To patients: Not tolerating lithium • Carbamazepine is less effective than lithium or valproate in acute mania • Used in • Acute mania or mixed states • Acute bipolar depression • Maintenance therapy Caution: • Not recommended in any woman of reproductive age • Aware of drug interactions LAMOTRIGINE • Anticonvulsant, best for Bipolar depression • It is now extensively used in the maintenance therapy of type II bipolar disorder, because the risk of inducing mania is minimal • Improved cognition, excellent tolerance, serious autoimmune rash • Valproate interaction • 75 - 300mg/day. TOPYRAMATE • Significant cognitive ill effect and paresthesia • Weight loss • 50 mg qhs, increase by 50 mg/wk. in divided doses to maximum of 200 mg bid GABAPENTIN • Anticonvulsant, new drug for bipolar but effect is not evident • Most helpful with anxiety, insomnia, pain • May cause persistent sedation • Excreted by kidneys only, no serious drug interactions reported • 1200 to 4000 mg/day. DoC for Acute Bipolar Mania Severe • Haloperidol (5-10mg IM) • Lorazepam (1-2mg IM) • Ziprasidone (10-20mg IM) • Olanzapine (10mg IM) • Aripiprazole (9.75mg IM) Mild to Moderate • • • • • • • • Lithium 600-1200mg/day Valproate 1200-3000mg/day Aripiprazole 15-30mg/day Quetiapine 400-800mg/day Risperidone 2-6mg/day Ziprasidone 80-160mg/day Haloperidol 5-20mg/day Lorazepam 10mg/day DoC for Acute Bipolar Depression •Assess for potential self-harm/inpatient •First line: Quetiapine or Lurasidone •Second line: •Olanzapine plus Fluoxetine •Valproate •Quetiapine or Lurasidone plus Lithium or Valproate •Lithium plus Valproate or Lamotrigine •Third line: •Lithium, Valproate, Carbamazepine •Mood stabilizer plus Fluoxetine or Bupropion •Refractory patients: •Electro-convulsive therapy •Severe suicidal intentions, psychosis, catatonia Conclusion: • Bipolar disorder requires long-term treatment. • Bipolar disorder is a chronic, relapsing illness. • Bipolar disorder need medication to prevent new episodes and stay symptom-free. There is more to treatment than medication. • Medication alone is usually not enough to fully control the symptoms of bipolar disorder. • The most effective treatment strategy for bipolar disorder involves a combination of medication, therapy, lifestyle changes, and social support. • It’s best to work with an experienced psychiatrist. Bipolar disorder is a complex condition. • Diagnosis can be tricky and treatment is often difficult. For safety reasons, medication should be closely monitored. A psychiatrist who is skilled in bipolar disorder treatment can help you navigate these twists and turns.