Mood and Bipolar Disorders

Mood Disorders & Bipolar Disorders

• Manic Episode: Requires abnormally elevated, expansive, or irritable mood, lasting at least one week, regardless of hospitalization, or any length if hospitalization is required.
  • DIGFAST Criteria: Distractibility, Impulsivity, Grandiosity, Flight of ideas, Activity/Agitation, Sleep disturbance, and Talkativeness.
  • Significant impairment, hospitalization, or psychotic features need to be present to confirm diagnosis.
• Hypomanic Episode: Requires abnormally elevated, expansive, or irritable mood, lasting at least four days, along with three or more DIGFAST symptoms (four if only irritable mood).
  • There's a noticeable change in functioning, the change is observable by others, psychotic features are absent, and no significant impairment or hospitalization is required.
• Mixed Episodes: Criteria for manic (or hypomanic) episode are met, concurrent w/ at least three symptoms of Major Depressive Episode (MDE).
• Mood Disorders: Marked by relapses w/ relatively normal functioning between episodes.
  • A first-degree relative w/ bipolar disorder increases the likelihood tenfold.
  • Earlier onset indicates a greater likelihood of psychotic features and a poorer prognosis.
  • Men and women are equally affected.
  • Onset typically occurs before age 30, w/ a mean age of 18 years for the first mood episode.
  • 25-50% of patients attempt suicide, and 10-15% die by suicide.
  • Cyclothymic Disorder: About 1/3 of patients eventually develop bipolar disorder, onset between ages 15-25.
• Bipolar I: one or more manic episodes, w/ or w/o major depressive episodes.
• Bipolar II: Requires one or more MDE's and at least one hypomanic episode.
• Cyclothymia: Hypomanic symptoms and periods of depression for at least two years in adults (one year for children/adolescents).
  • Symptoms do not meet the criteria for manic or major depressive episodes & symptoms do not cease for more than two months.
• Rapid Cycling Specifier: At least four mood episodes within 12 months.
• Major Depressive Episode (MDE): requires five or more symptoms (SIGECAPS) for at least two weeks and includes Sleep disturbances, loss of Interest, feelings of Guilt, Energy loss, Concentration issues, changes in Appetite, and Suicidal thoughts.
  • At least one symptom must be either depressed mood or anhedonia (loss of interest/pleasure).

Bipolar Disorder Pharm

• Acute Mania: Lithium combined w/ an antipsychotic.
  • Valproate with an antipsychotic can be a reasonable alternative with aripiprazole, haloperidol, olanzapine, quetiapine, and risperidone.
• Carbamazepine demonstrates similar efficacy with mood stabilizers in monotherapy vs AP.
• Valproate and carbamazepine are particularly effective for the rapid cycling and mixed episodes.
• Never use antidepressants (ADS) as monotherapy, as they can activate mania.
• Maintenance Therapy: The same regimen that was effective acutely, plus therapy like supportive psychotherapy, family therapy, or group therapy.

Lithium

• MOA: Inhibits 5HT/NE reuptake and second messenger systems.
  • Decreases suicide risk, Kidney metabolism, Avoid if CrCl <30mL/min.
• Pre-lithium Workup: Requires SCr, electrolytes, TSH, weight, UPT, CBC, & EKG.
• ADRs: Hypothyroidism, tremor, weight gain, leukocytosis, GI issues (N/V/D, metallic/salty taste, dysgeusia), dermatologic issues including acne vulgaris & psoriasis.
  • Cardiac arrhythmia (bradycardia, abnormal T waves, edema), CNS issues including sedation, lethargy, ataxia, slurred speech, and HA.
• Duration-related ADRs include Nephrogenic diabetes insipidus, hyperparathyroidism & hypercalcemia, interstitial nephritis, polyuria/polydipsia.
• Monitoring: BUN/Cr, electrolytes/calcium, TSH/PTH, and lithium levels checked every 1-3 months; during treatment.
• Pregnancy: Ebstein's anomaly linked w/ use (especially in the first trimester).
• ↑ Lithium Levels: salt, ACE I/ARBs, diuretics, NSAIDs.
• ↓ Lithium Levels: caffeine and theophylline.
• Neurotoxicity: co-administration w/ Verapamil, diltazem, phenytoin, & carbamazepine.
• Warnings/Cautions include Pseudotumor cerebri, serotonin syndrome, myasthenia gravis.
• BOXED WARNING: Toxicity; closely monitor lithium serum levels, especially severe toxicity (>2.5mEq/L) requiring seizure.
  • Mild toxicity (<1.5mEq/L) causes fine tremor, weakness, and mild ataxia.
  • Moderate (1.5-2.5mEq/L) includes Coarse tremor, vomiting, confusion, and nausea.
  • Severe (>2.5mEq/L) includes tonic-clonic seizures that cause severe vomiting, confusion, and neurological risks.

Valproate

• MOA: Blocks Na channels and increases GABA.
• Formulations: valproic acid, valproate sodium, divalproex sodium.
• Clinical Point: Ineffective for acute mania, better for bipolar depression.
• ADRs: Alopecia, Gl disturbances, tremor, diplopia, PCOS.
  • Dose-related: CNS symptoms like dizziness, sedation, tremor, and HA; thrombocytopenia.
  • Non-Dose-Related: Hepatotoxicity, hyperammonemia & encephalopathy, SJS/TEN/DRESS, pancreatitis.
• Contraindications: Hepatic Dysfunction, Pregnancy.
• Drug Interactions: Increases lamotrigine levels.
• Monitoring: LFTs, CBC, and ammonia levels (if lethargy, vomiting, hypothermia).
• Therapeutic Range: 50-100mcg/mL.
• BOXED WARNINGS: Hepatotoxicity, fetal risk (neural tube defects), pancreatitis.

Lamotrigine

• MOA: Inhibits glutamate release/Na channels.
• ADRs: Nausea, fatigue, ataxia, dizziness, sedation, and back pain. Potential for Aseptic meningitis (rare) blood dyscrasias and hemophagocytic lymphohistiocytosis.
• Therapeutic Range: 1-5 mcg/mL.
• BOXED WARNING: SJS/TEN/DRESS.

Carbamazepine

• MOA: Blocks Na channels, effective as monotherapy for mixed Episodes.
• ADRs: N/V/C, ataxia, dizziness, sedation, and blurred vision.
• Significant ADRs: Hematologic issues (aplastic anemia, leukopenia, thrombocytopenia), cardiac issues, and hepatotoxicity.
  • SIADH and hyponatremia are dose-related.
• Monitoring: CBC w/ diff, LFTS, BUN/Cr, UA, sodium, eye exam/IOP, & UPT; UPT.
• Therapeutic Range: 4-12mcg/mL. Toxic Levels >12-15mcg/mL.
• DIs: CYP3A4 & 1A2 inducer & CYP 3A4 substrate (autoinduces metabolism), autoinduction indicates may need for dose increases.
• BOXED WARNINGS: SJS/TEN & HLA-B*1502 (screen Asian), aplastic anemia & agranulocytosis & pregnancy.
• Synergistic w/ lithium for refractory bipolar.
• CI: CYP450 with grapefruit juice, protease inhibitors, azoles.

Oxcarbazepine

• Better tolerance, same efficacy
• Monitor Na levels.
• Fewer Rash/hepatotoxicity.