Bipolar Disorder (BPD) Treatment: Lithium & Medication - PDF

BPD I/II/ Cyclothymia Rapid Cycling Four or more discrete affective episodes per year (either depressive or manic) Faster or more often with shorter time period in between episodes Tend to have a longer duration and a more refractory course, “rapid relapsing” When diagnosing rapid cycling, t...

BPD I/II/ Cyclothymia Rapid Cycling Four or more discrete affective episodes per year (either depressive or manic) Faster or more often with shorter time period in between episodes Tend to have a longer duration and a more refractory course, “rapid relapsing” When diagnosing rapid cycling, the number of affective episodes, rather than cycles, is counted. Can also occur with hypomania and dysthymia Substance abuse (particularly cocaine) can mimic rapid cycling 02/11/2025 24  BPD I/II/ Cyclothymia Rapid Cycling About 50% of bipolar patients - Women making up 80–95% of rapid-cycling patients Other risk factors: - Treatment with antidepressants alone - Development of clinical or subclinical hypothyroidism (spontaneously or during lithium treatment) Lithium and lamotrigine (L and L) combination is superior to either one alone in treatment sensitive rapid cycling bipolar 02/11/2025 25 BPD with Mixed Features 26 02/11/2025  BPD I/II/ Cyclothymia with Anxious Distress Must have ≥ 2 of the following symptoms the majority of days during an episode - Irritable, short-fused or “keyed up” - Restlessness - Difficulty concentrating due to worry - Feeling of dread/ impending doom - Fear of “loosing control” 02/11/2025 27 BPD I/II with Psychotic Features Can occur during depressive or manic episodes Delusions: false beliefs that cannot be real Extreme paranoia Hallucinations: auditory, visual, tactile, olfactory, gustatory Catatonia Small percentage of patients 02/11/2025 28 BPD and Related Disorders Differential Diagnosis Delirium Dementia Substance-related disorders Schizophrenia Schizoaffective disorder Delusional disorders Factitious disorder Malingering Attention-deficit/hyperactivity disorder Conduct disorder Schizoid Personality Disorder (PD) Borderline PD Histrionic PD 29  Medications That Can Cause BPD Symptoms Isoniazid Corticosteroids Procarbazine (cancer Metoclopramide chemo) Cimetidine Decongestants Sympathomimetic amines - ADHD medications Bronchodilators Disulfiram Procyclidine/ L-Dopa TCAs Street drugs/ Caffeine/ Caffeinated sports Hallucinogens drinks Benzodiazepines 02/11/20 25 30  Endocrine/ Nutritional Causes of BPD Symptoms Hemodialysis Vitamin B12/ folate deficiency Addison disease Hyper/ hypothyroidism 02/11/2025 31  Neurologic Causes of BPD Symptoms Multiple sclerosis Traumatic brain injury Seizure disorders Huntington disease Post stroke Benign/ malignant brain neoplasms 02/11/2025 32 Infectious Causes of BPD Symptoms Neurosyphilis Herpes simplex encephalitis HIV infection 02/11/2025 33  BENZODIAZEPINES 34 02/11/2025 LIFE STYLE CHANGES  BPD Treatment: Lithium First medication developed to treat BP disorder in the 1940’s MOA unknown: multiple theories - “Strengthens the calm neurons and calms the excited neurons” Most efficacious in classic BPD 02/11/2025 35  36 02/11/2025 BPD Treatment: Lithium Takes 5-10 days to take effect - Antipsychotic and/or benzodiazepine used for the initial treatment of mania until lithium takes affect Prevents relapse (not 100%) Reduces the risk of suicide Reduces aggression/ impulsivity Reduces the risk of developing neurocognitive disorder Increase in gray matter and hippocampus in patients taking lithium 02/11/2025 37 Lithium Treatment and Monitoring The trough blood level should be adjusted and maintained between 0.6–1.2 mmol/L. (“lithium one.2”) - Check serum trough level, right before next dose - Narrow therapeutic index: toxic levels can be fatal and can be close to therapeutic levels Contraindicated: significant renal impairment, sodium depletion, dehydration, significant cardiovascular disease, hypothyroidism, pregnancy. Read the package insert! 02/11/2025 38  Lithium Side Effects LMNOP Lithium Movement (tremor/ neuro symptoms) Nephrotoxicity (and diabetes insipidus) hypOthyroidism Pregnancy: teratogenic, increased risk of Ebstein’s anomaly (LIThium: low implanted tricuspid) “Twitchy (GI and neuro) and pissy” (renal and diabetes insipidus) 02/11/2025 39 Lithium Side Effects Nausea, diarrhea Polyuria and thirst Weight gain Edema Worsening psoriasis Cognitive impairment.. and others With over-dose, worsening neuro symptoms: ataxia, seizures, coma, death 02/11/2025 40 Circumstances That Can Change Lithium Serum-levels ↑↓Medical illness, especially with diarrhea, vomiting, or anorexia ↑↓Surgery: metabolic aberrations ↑ Severely restrictive dieting, sodium restriction diet (inverse proportion) ↓ With increased sodium intake ↑ Strenuous exercise/ increased perspiration, dehydration, hot climate ↑Advanced age Pregnancy and delivery and teratogenic Inverse relationship to sodium level: higher the sodium, lower the lithium level and visa versa 41 02/11/2025 Labs Prior to Initiating Lithium CBC with differential Comprehensive metabolic panel UA BUN/ Creatinine TSH/ Thyroid function studies Calcium Pregnancy test for women of childbearing potential ECG for patients > 40 or ↑CV risks 42 Managing Side Lithium Side Effects Watchful waiting – tolerance to some side effects (eg, nausea and tremor) can occur, but unlikely with weight gain Changing the time of administration Lowering the dose (dose reductions risk compromising efficacy) Changing to a different lithium formulation (immediate or slow release). Dividing the daily dose to take smaller amounts more often, to decrease peak serum levels. Discontinuing and switching to an anticonvulsant if side effects are intolerable 02/11/2025 43  Lithium Drug Interactions: Epocrates!! Exam Drug Interaction Question Increases lithium level Thiazide diuretics Nonsteroidal anti-inflammatory drugs (except aspirin) Angiotensin converting enzyme inhibitors Antibiotics tetracyclines and metronidazole Decreases lithium level Potassium-sparing diuretics May increase or decrease lithium level Loop diuretics 02/11/2025 44  BPD Treatment (Tx): Anticonvulsant Drugs Decreases firing of CNS nerves - Inhibits voltage gated sodium channels Increases GABA - Calming, mechanism of action (MOA) of hypnotics/ tranquilizers 02/11/2025 45 BPD Tx: When to Use Anticonvulsants Alternative to, or previous poor response to, lithium Recurrent substance abuse All are teratogenic 02/11/2025 46  BPD Tx: Valproic Acid/ Divalproex (Depakote) Some sources consider DOC (drug of choice) Used for rapid cyclers: valproic Monitor blood levels: therapeutic range Side effects: weight gain, nausea, vomiting, hair loss, easy bruising, and tremor, drowsiness, fatigue, skin rash, gait disturbance Divalproex is enteric coated, contains valproic acid and valproate, better on GI track, more expensive 47  Valproic Acid/ Divalproex (Depakote) PATHological Side Effects Pancreatitis Aplastic anemia risk/ low platelet count Teratogenic: neural tube defect and others - Valpro ATE the folate Hepatic toxicity potential: hepatic failure risk 48 Valproic Acid Lab Monitoring Liver Enzymes (ALT, AST) 2 weeks, 4 weeks, 3 months, annually CBC with differential and as above platelets Glucose as above Weight as above Valproate levels Lipase If symptomatic: pain, nausea, vomiting Don’t need to know schedule for exam. Need to know labs patient needs for monitoring 02/11/2025 49 Carbamazepine (Tegretol) Indicate for mixed features or as an alternative medication Side effects: Diplopia and ataxia (most common) GI (N/V/D), weight gain,, hyponatremia, rash, pruritus, elevated liver enzymes Photosensitivity “Take Control of mixed features” 50 Carbamazepine (Tegretol) Blood dyscrasias - Aplastic anemia, leukopenia Life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), especially the first 8 weeks of therapy. - Screen Asian patients for HLA-B*1502 Check labs as per valproic acid 51 BPD Treatment: Lamotrigine (Lamictal) Used for predominately depressive BP 1 or 2 or rapid cycling Weight loss properties SJS/ TEN “treat the “lows” with lamotrigine” 02/11/2025 52  BPD Psychosis/ Agitation/ Depression Tx Only 5 FDA-approved for bipolar: cariprazine (Vraylar®), lurasidone (Latuda®), olanzapine-fluoxetine combination (Symbyax®), quetiapine (Seroquel®), and lumateperone Caplyta®) Combo: fluoxetine and olanzapine combo (Symbyax) - Olanzapine: anti-psychotic, significant weight gain Quetiapine (Seroquel) - Antipsychotic - Recent FDA approved single treatment for mania and depression 02/11/2025 53 BPD Agitation/ Insomnia Treatment Benzodiazepines - clonazepam or lorazepam Sleep hygiene Low dose trazadone Insomnia a risk factor for BPD 02/11/2025 54 BPD: Electroconvulsive Therapy For recalcitrant/ difficult to control cases Very effective 02/11/2025 55  Bipolar Disorder Treatment in Pregnancy First generation antipsychotic medications - Haloperidol (Haldol) ◦ Relatively safe ◦ Extrapyramidal and uncomfortable side effects risk Second generation antipsychotic medication - Enroll in National Registry for Atypical Antipsychotics - Safer than lithium/ anticonvulsants Bipolar Disorder Treatment in Pregnancy ECT - Safe, effective Lithium: teratogenic especially in the first trimester - Timing of medication during pregnancy, pregnancy planning - Use with close follow up, ultrasound Follow by psychiatrist and perinatologist Name Duration Characteristics Psychotic Functioning Maintenance symptoms Treatment Bipolar I Manic Sx for at Manic episodes and Possible Usually impaired Lithium or least 1 week almost always on either spectrum Anticonvulsant/ depression; mood stabilizers, Can have euthymia SGA, lamotrigine if depressive Bipolar II 3 mania Hypomania/ depression No Hypomania: no As for BP I symptoms for 4 Depression can be significant social days debilitating/ worse in or occupational BP II dysfunction Cyclothymia Present for 2 Increased mood (does No Symptoms do not Treatment if years not meet hypomania interfere with work problematic Never symptom characteristics) and or social free for more dysthymia functioning than 2 months (PDD) Rapid Four or more Faster/ shortened time Possible Usually impaired Divalproate or cyclers discrete affective period between episodes on either spectrum lamotrigine/ lithium episodes/ year or as for BP I BPD mixed Concurrent symptoms of Possible Usually impaired Carbamazepine or features mania/ depression and labile as for BP I Bipolar Treatment: Primarily Depression Anti-depressants alone mostly ineffective Risks a manic attack 02/11/2025 59 BPD Tx: Breakthrough Symptoms If on lithium or mood stabilizer and blood levels are therapeutic, add SGA: - Quetiapine (Seroquel) 02/11/2025 60 BPD Treatment Adherence/ Compliance Approximately 50% of patients stop medication - Average time to non-adherence: 9 months Cost, side effects, hate taking meds Some bipolar artists feel their creative work is stifled Emotional blunting with medication If lithium is withdrawn abruptly, approximately 50% of patients relapse within 5 months. 02/11/2025 61