Riding the Waves: Tools for the Management of Bipolar Disorder Jacintha S. Cauffield, Pharm.D., BCPS, CDE Associate Professor of Pharmacy Practice Palm Beach Atlantic University Lloyd L. Gregory School of Pharmacy West Palm Beach, FL
Bipolar Disorder: What are We Treating? Depression Mania Bipolar Disorder Elevated Mood + Increase in energy or goal directed activity
Treatment Course Phases Relapse 0 months 2 months 6 months Recurrence Acute Continuation Maintenance CNS Drugs 2011; 25 (10): 819-827
Mood Stabilizers: Cornerstone of Therapy Effects in both acute and maintenance phases of treatment At least partial amelioration of mania and depression Distinguished from first generation antipsychotics (FGAs; typical antipsychotics)
Mood Stabilizers: First Line Agents Lithium Antiseizure Drugs Second Generation Antipsychotics (SGAs) Gold standard Carbamazepine Lamotrigine Valproate Effects depend upon agent Guidelines vary on specific agents
Neuroprotective effects Anti-suicide effects Best for euphoric mania High noncompliance rate Side effects in 75% Lithium Discontinuation-induced refractoriness 1/5 of patients
Lithium Liabilities: Side Effects Side Effect Central Nervous System (CNS) Toxicity (40%; headache, memory impairment, confusion, difficulty concentrating, impaired motor coordination) Skin effects (acne, psoriasis, rash) Frequent urination (diabetes insipidus) GI (nausea, vomiting, diarrhea) Kidney damage (10-20%?) Thyroid dysfunction (35%; Hypothyroidism) Tremor (hand; 50%; dose-dependent) Methods to Alleviate Minimize dose Temporarily stop medication or switch agents Minimize dose; single bedtime dose; thiazide or loop diuretics (with lithium dose reduction) Take with food, minimize dose, extended release formulation Adequate hydration, minimize dose, once daily dosing, avoid toxicity Levothyroxine Minimize dose, beta blocker
Lithium Liabilities: Drug Interactions and Lifestyle Effects Drug High blood pressure medications ACE inhibitors (lisinopril) Angiotensin Receptor Blockers (ARBs) Diuretics ( water pills ) Caffeine Carbamazepine Dehydration FGAs NSAIDs Salt Effect Lithium concentrations Lithium concentrations CNS side effects Lithium concentrations Lithium worsens movement disorders (EPS) Lithium concentrations Increased intake Lithium concentrations
Divalproex (Valproic acid; Depakote) Most prescribed mood stabilizer in the US With the exception of SGAs Can be used for: Mania Mixed States Depression More effective than lithium for: Rapid cycling Mixed episodes Substance Use Disorder Can be used with both lithium and carbamazepine
Divalproex: Drawbacks Low platelet counts Dose-related >110 mcg/ml in women, >135 mcg/ml in men Hair loss Reversible Dose related? Liver toxicity children <2 years old Monitor liver function Pancreatitis 1-5% incidence Weight Gain
Carbamazepine Not first-line; Used for: Lithium nonresponders Mixed states Rapid cyclers
Carbamazepine: Monitoring Reaction Monitoring/Action Quick Facts Low blood counts* Monitor CBC Rare Dizziness, gait disturbances Minimum effective dose Serum concentration 4-12 mcg/ml Low sodium Monitor electrolytes More common in elderly Weakness, mental status changes Worse with oxcarbazepine Nausea Give with food Use controlled release formulation Dose-dependent Resolves with time Rash* Test for HLA-B*1502 High risk population: Asian Risk highest in first few months *Black box warnings
Lamotrigine Antidepressant Effects Mania Effective in prevention of bipolar depression; used frequently for type II Superior to lithium for depression, inferior for mania Role in acute bipolar depression less clear; small effect size No evidence for role in acute mania or mixed-type episodes
Lamotrigine Dosing Alone With Valproate With inducer (carbamazepine, phenytoin, etc.) Weeks 1-2 25 mg daily 25 mg every other day 50 mg daily Weeks 3-4 50 mg daily 25 mg daily 100 mg daily Week 5 100 mg daily 50 mg daily 200 mg daily Week 6 200 mg daily 100 mg daily 400 mg daily Skin rash in lamotrigine o Greater risk given with divalproex and/or aripiprazole If off more than a few days, must restart titration
Antipsychotics: Two Classes First Generation Antipsychotics (FGA) Typical Antipsychotics (Selected) Chlorpromazine (Thorazine) Fluphenazine (Prolixin) Haloperidol (Haldol) Perphenazine (Trilafon) Second Generation Antipsychotics (SGA) Atypical Antipsychotics Aripiprazole (Abilify) Asenapine (Saphris) Brexpiprazole (Rexulti) Cariprazine (Vraylar) Clozapine (Clozaril) Iloperidone (Fanapt) Lurasidone (Latuda) Olanzapine (Zyprexa) Paliperidone (Invega) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon)
Low Potency FGAs High Potency Examples Thorazine (chlorpromazine) Haldol (haloperidol) Prolixin (fluphenazine) Trilafon (perphenazine) Anticholinergia (dry mouth, dry eyes, difficulty peeing, constipation) More Less Weight gain More Less Dizziness when standing up More Less Sedation High Low Hyperprolactinemia Low High Movement Disorders (Extrapyramidal Symptoms; EPS) Less More
FGAs: All Have EPS Acute Dystonias Severe Muscle Contractions Pseudo-Parkinsonism Slowing of movements Akathisia Inability to sit still Tardive Dyskinesia Repetitive Involuntary Movements
Second Generation Antipsychotics: How are They Different? Less EPS (although some agents do have some) Akathisia Pseudo-Parkinsonism Incidence of tardive dyskinesia is very low Hyperprolactinemia Except Risperdal and Invega Better mood stabilizing abilities Side effect profiles vary more Weight gain Diabetes mellitus
Weighing Side Effects Against Benefits (Example: Antipsychotics) Medication Sedation Weight gain/ Diabetes Abilify (Aripiprazole) Low Low High Vraylar (Cariprazine) Low Low High Latuda (Lurasidone) Low Low High Zyprexa (Olanzapine) High High Low Invega (Paliperidone) Low Medium High Seroquel (Quetiapine) High Medium Low Risperdal (Risperidone) Low-Medium Medium High Zyprexa (Ziprasidone) Medium-High Low Low Akathisia / Movement disorders
Antipsychotic Use in Bipolar Phases Acute Mania: Aggression/Psychosis* Acute Mania Depression Maintenance Abilify (Aripiprazole) IM (ODT) Yes Yes (Depot Injection) Saphris (Asenapine) Yes (sublingual tablet) Vraylar (Cariprazine) Yes Latuda (Lurasidone) Yes Zyprexa (Olanzapine) IM/PO/ODT Yes Yes (Depot Injection) Invega (Paliperidone) ER only (Depot Injection) Seroquel (Quetiapine) PO Yes Yes Yes Risperdal (Risperidone) PO/ODT Yes Yes (Depot Injection) Geodon (Ziprasidone) IM Yes IM; IM=Intramuscular; ODT=Orally dissolving tablet; ER=extended release; PO= oral Bipolar Disorders 2013:15:1-44
Selecting a Mood Stabilizer Lithium Valproate Euphoric mania Previous lithium response Few episodes of illness No psychotic symptoms Mixed state (Dysphoric) Rapid cycling Multiple prior episodes Comorbid substance use disorder
Benzodiazepines (Xanax, Klonopin) Restrict to acute mania with: Agitation Anxiety Panic Insomnia Some SGAs are as effective in the acute setting IM injection Dispersible tablets Given high comorbid substance abuse in bipolar disorder, minimize use Taper and d/c as soon as possible
ipolar Depression
Bipolar Depression: Acute Polypharmacy is common practice Approved Agents Latuda (lurasidone) Seroquel (quetiapine) Zyprexa (olanzapine) + Prozac (fluoxetine) All three have similar efficacy
What About Antidepressants? Most commonly used agents for bipolar depression Heavily debated Clinical data to support recommendations is sparse Two main issues: Risk for switching Efficacy
Antidepressants: Risk for Switching to Mania Highest High Lowest Tricyclic antidepressants Elavil (amitriptyline) Nortriptyline, desipramine, imipramine SNRIs Cymbalta (duloxetine) Effexor (venlafaxine) SSRIs Prozac (fluoxetine), Paxil (paroxetine) Bupropion
Guidance for Using Antidepressants Appropriate: In individual patients With h/o positive response If a patient relapses off of an antidepressant Avoid: Monotherapy in type 1 In mixed episodes With > 2 manic symptoms concomitant with psychomotor agitation or rapid cycling In patients with h/o switching on antidepressants
Putting Together a Medication Regimen: Bipolar DO Lamotrigine (careful with valproate) Lurasidone Quetiapine Olanzapine + fluoxetine Lithium Valproate Antipsychotics Depression Mania Bipolar Disorder
Why do I need medication?
Mental illness can only be treated, not cured Pneumonia + medication = cure The bacteria causing the infection don t belong there Medication kills the bacteria Once we kill them off, they don t come back Diabetes + medication = control The cause of diabetes has to do with how the body works Medication balances the body If we take the medication away, the imbalance returns
How does someone feel when they are sick?
Treatment Plan Medication Therapy Self Care Healing
Medications relieve symptoms so that you can care for yourself.
Therapeutic Balance Ideally: no symptoms with no side effects Reality: must balance SYMPTOM CONTROL MEDICATION SIDE EFFECTS
Prognosis Best predictor is medication adherence 50% of patients d/c medication due to intolerable side effects 2/3rds receive inadequate treatment due to lack of insight Prognosis worse with: Substance Use Disorder Comorbid psychiatric diagnoses Treat early and fast to maximize chances of relapse prevention doubles rate of medication response
What are the challenges of taking medications?
They take time to work. Most medications take 1-2 weeks to begin working. Many do not give significant relief for 4-6 weeks, sometimes up to 3 months. If you are experiencing side effects, it s easy to get frustrated and stop taking your medication.
The idea of taking medications is scary. It s not natural. I should be able to manage this on my own. So many side effects. What s going to happen to me if I take this for a long time?
Weight gain Sleepiness Sexual dysfunction Is it a side effect, or is it my illness? Some side medication side effects are similar to those of untreated mental illness Some side effects go away Nausea Some sedation Headaches Give the medication time to work. Communicate closely and honestly with your provider.
Dry mouth Coping with side effects Sip water or sugar free drinks Chew sugar free gum Use sugar free candy (sparingly) Drowsiness Take medication at bedtime if possible Nausea take with food Constipation eat a high fiber diet and drink plenty of water