Bipolar Medication

# BIPOLAR DISORDERS & MEDICATIONS
INTRODUCTION

  • Presentation by Dr. Asma Perveen.

CASE STUDY 1: DISCUSSION

  • Subject: Joey

  • Age: 32, previously seen for therapy after his mother's death.

  • No other known psychiatric history.

  • Family History:

    • Mother hospitalized twice for unspecified mental illness.

    • Paternal uncle committed suicide at age 14.

  • Personal Life:

    • Married for 10 years, has two children.

    • Recently became a partner in a law firm.

    • Describes himself as skilled in athletics and music.

  • Current Issue:

    • Experienced feelings of anxiety and stress.

    • Display of behavior during visit:

    • Loud and demanding for immediate consultation due to perceived time value.

    • Attempted to distribute business cards in the waiting room.

    • Appearance: disheveled and unshaven.

    • Expressed fear of going to work without elaboration.

    • Pacing during consultation, unable to remain seated.

    • Hours worked recently: until 2:00 A.M. for a significant case, expressed desire for fame.

    • Observed pressure in speech and tangential thought process.

    • Admitted to needing “a couple of drinks” daily for calming down.

DIFFERENTIAL DIAGNOSIS

  • Bipolar Disorder Type 1 (BP1):
    An episode of mania sufficient for diagnosis, irrespective of depressive history.

  • Criteria for Mania:

    • Defined as a distinct period of abnormally and persistently elevated mood and increased energy or goal-directed activity.

    • Duration: at least one week (or any duration if hospitalization required).

    • Severity can be mild, moderate, or severe.

ASSOCIATED DIAGNOSTIC CRITERIA OF MANIA

  • Classic Mania Symptoms (more straightforward to diagnose):

    • Racing thoughts, pressured speech, grandiosity, increased energy, goal-directed activity, engaging in pleasurable activities, distractibility, decreased need for sleep.

    • Outcomes: marked social or occupational impairment, possible hospitalization, or psychotic features.

  • Hypomania:

    • Lasting at least four consecutive days characterized by observable change in energy or activity and mood disturbances uncharacteristic of the individual.

    • Elevated or irritable mood, increased activity levels.

    • No significant impairment or hospitalization required.

MEDICAL CONDITIONS ASSOCIATED WITH MANIA

  • Various health issues may induce or exacerbate mania:

    • Central nervous system trauma (e.g., post-stroke).

    • Metabolic disorders (e.g., hyperthyroidism).

    • Infectious diseases (e.g., encephalitis).

    • Seizure disorders.

    • Central nervous system tumors.

SUBTYPE DIFFICULTIES

  • Challenges in differentiating bipolar subtypes:

    • Seasonal patterns.

    • Substance use issues.

    • Characterological issues.

    • Onset of mania can be either abrupt or gradual.

    • Reference: Acute mania stages by Carlson and Goodwin (1973).

STAGES OF ACUTE MANIA

  • Stage 1 (Hypomania):

    • Increased psychomotor activity, emotional lability, euphoria, or grandiosity.

    • Coherent yet tangential thinking.

  • Stage 2 (Frank Mania):

    • Elevated psychomotor activity, heightened emotional lability, possible hostility and impulsivity, cognitive disorganization, possible delusions.

  • Stage 3 (Severe Mania):

    • Frenzied activity, incoherent thought processes, disorientation, potentially florid psychosis.

DIAGNOSTIC EXCLUSIONS IN DIFFERENTIAL DIAGNOSIS

  • Distinguishment from:

    • Attention Deficit/Hyperactivity Disorder (ADHD).

    • Schizophrenia.

    • Personality disorders.

    • PTSD.

FACTS ON BIPOLAR DISORDER

  • Lifetime prevalence:

    • Bipolar Type I: 1%

    • Bipolar Type II: 4%

  • Incidence of psychotic features:

    • 47% to 75% among those diagnosed.

  • Positive family history risk: 60% to 65%.

  • Gender ratio:

    • Bipolar I: 1:1

    • Bipolar II: 1:2

  • Socioeconomic context:

    • Overrepresented in higher socioeconomic and educational groups.

  • First episodes:

    • Males typically present with mania; females typically present with depression.

  • Age of onset:

    • Typically between 20 and 40 years.

    • Average onset: 20 years.

    • Symptoms may appear in adolescence or childhood.

BIPOLAR DISORDER CLASSIFICATIONS
BIPOLAR I DISORDER

  • One or more episodes of mania.

  • Possible preceding or subsequent hypomanic or depressive episodes.

  • Depressive episodes must meet criteria for major depression.

  • Individuals may remain asymptomatic between episodes, though functional impairment may persist.

  • Age factors:

    • Increasing age correlates with more frequent and prolonged episodes.

  • Mixed states:

    • Variable symptoms pattern in mood, thought, and motor activity recognized in DSM-5 as a discrete clinical entity (30% prevalence).

    • Mixed states often more severe, chronic, and difficult to treat than pure manic or depressive episodes.

BIPOLAR II DISORDER

  • At least one depressive episode and one hypomanic episode.

  • Difficult to differentiate from major depression due to:

    • Patients may not recognize elevated mood as dysfunctional and often exhibit irritability.

    • Clinician assessment variance is common for hypomania.

    • Symptoms, while not as severe as Bipolar I, can be chronic and disabling with a suicide risk.

CASE STUDY 2: PLENARY DISCUSSION

  • Subject: Cheryl R.

  • Age: 28, married with two children under three.

  • Referred by family doctor.

  • Current treatment: fluoxetine 20 mg daily.

  • Patient history: no hospitalizations, never in therapy.

  • Symptoms: “lifetime of sadness,” periodic suicidal ideation in late adolescence, moderate improvement since starting fluoxetine.

  • Persistent symptoms include:

    • Irritability, tearfulness, tiredness, initial insomnia.

    • Concerns about parenting effectiveness.

    • Desires more “good days” lasting about a week every three months, during which she engages productively in crafting, socializing, and exercising.

DIAGNOSTIC SPECIFIERS

  • Based on episode severity, remission status, and mixed features:

    • With anxious distress, rapid cycling, melancholic features, atypical features, and psychotic features.

    • Including peripartum onset and seasonal pattern.

MIXED EPISODES

  • Definition: Mania or hypomania with depressive features or a depressive episode with manic or hypomanic features.

  • Risk of antidepressants inducing mania; pairing with mood stabilizers advised.

  • Volatile disagreement on antidepressant recommendations for sequential treatment courses exists.

RAPID CYCLING

  • Defined as at least four episodes of mania, hypomania, or major depression in the previous twelve months.

  • Estimated prevalence: 10% to 20% of bipolar patients; predominantly women.

  • Associated factors include:

    • Hypothyroidism, neurological conditions, head injuries, intellectual disabilities, substance abuse.

    • Characterological features: Characterized by poor lithium response and correlation with antidepressant use.

    • Generally indicative of poor prognosis.

CYCLOTHYMIC DISORDER

  • Many periods of alternating depressive and hypomanic symptoms for at least two years; does not meet criteria for major depression or hypomanic episodes (subthreshold).

  • Symptoms present at least half the time, never absent for over two months.

  • Social or occupational impairments may occur during depressive phases but typically not during hypomanic periods.

  • Chronic nature; about one-third of individuals may develop major affective disorders.

MOOD DIAGRAM

  • Chronic swings in mood & energy fluctuating between hypomanic and depressive symptoms, typically presenting in adolescence.

TREATMENT STRATEGIES

  • Lifestyle Changes:

    • Relaxation techniques, avoidance of triggers, support groups.

  • Psychotherapy:

    • Cognitive-behavioral therapy.

  • Medications include:

    • Mood stabilizers, antidepressants, antipsychotics, and anti-anxiety medications.

CRITERIA FOR CYCLOTHYMIA DISORDER

  • Numerous alternating depressive and hypomanic symptoms not meeting criteria for full episodes.

  • Not attributable to organic factors or other psychiatric disorders.

OTHER BIPOLAR DIAGNOSES

  • Include:

    • Substance/medication-induced bipolar disorder.

    • Bipolar disorder due to another medical condition.

    • Unspecified bipolar disorder.

DIAGNOSIS CHALLENGES

  • Complexities in patient assessment, treatment planning, and education regarding bipolar spectrum disorders.

ETIOLOGY

  • Numerous theories focusing on neurobiology and genetic transmission rather than prevalent environmental influences.

  • Historical progression of research into neurotransmitters, synaptic activity, and homeostatic mechanisms.

THEORIES OF BIOLOGICAL BASIS
Dysregulation Theory (Rosenthal et al. 1986)

  • Mood regulation via multiple homeostatic mechanisms; dysfunction results in mood symptoms.

Chaotic Attractor Theory (Crutchfield et al. 1986)

  • Explains unpredictability in bipolar disorder due to biochemical defects causing neurotransmitter dysregulation.

Kindling Theory (Ballenger and Post 1980)

  • Cumulative biochemical changes in the limbic system lead to symptomatic presentation over time.

Catecholamine Theory

  • Examines noradrenergic abnormalities based on norepinephrine concentrations.

HPA AXIS HYPOTHESIS

  • Overactivation of the HPA axis potentially linked to transitions in mixed states and bipolar depression.

CALCIUM SIGNALLING THEORY

  • Abnormalities in calcium signaling and explorative neuroanatomical theories related to neuronal cell counts and neural resilience.

TREATMENT OVERVIEW

  • Evidence emphasizes bipolar disorder as biologically based, necessitating pharmacological intervention as primary treatment modality.

  • Consideration of combination therapies (mood stabilizers, psychotherapy, family group therapy).

INITIAL PHARMACOTHERAPY

  • Historical preference for lithium; emergence of anticonvulsants like carbamazepine and valproic acid.

  • Regimen adjustments to include mood stabilizers, antidepressants, and adjunct medications due to treatment complexities and response variances.

RECOMMENDATIONS FOR TREATMENT

  • Comprehensive medication management, side effect monitoring, maintenance treatment, and relapse prevention.

LITHIUM

  • Historically used for varying conditions; established as an effective treatment for acute mania and prevention of episodes.

  • Response rates: estimated at 60% to 80%.

  • Therapeutic dose: narrowly defined; adjustments necessary based on symptom stage and blood concentration.

MECHANISM OF ACTION OF LITHIUM

  • Neurotransmitter Modulation:

    • Enhances inhibitory neurotransmission (GABA) and reduces excitatory neurotransmission (Glutamate/Dopamine).

  • Phosphoinositide Metabolism:

    • Inhibits the enzyme inositol monophosphatase, depleting intracellular inositol and dampening overactive signaling pathways.

  • Second Messenger Systems:

    • Lithium inhibits Glycogen Synthase Kinase-3 (GSK−3GSK-3), which plays a role in neuroprotection, neuronal architecture, and circadian rhythm regulation.

  • Neuroprotective Properties:

    • Increases levels of Brain-Derived Neurotrophic Factor (BDNFBDNF) and helps protect neurons from excitotoxicity.

SIDE EFFECTS OF LITHIUM

  • Common adverse effects: gastrointestinal (nausea, vomiting), nervous system (tremors), endocrine (thyroid issues), renal dependence for elimination, cardiovascular impacts.

  • Monitoring of blood levels crucial during treatment and dosage adjustments.

ANTICONVULSANTS

  • Overview of medications (e.g., carbamazepine, divalproex) and their dosing protocols with emphasis on monitoring for side effects.

  • Distinctions between older and newer agents, highlighting lamotrigine's role in treating bipolar depression.

MECHANISM OF ACTION OF ANTICONVULSANTS

  • Valproic Acid / Divalproex:

    • Facilitates GABAergic transmission by inhibiting GABA transaminase (the enzyme that breaks down GABA).

    • Blocks voltage-gated sodium channels to stabilize neuronal membranes and prevent repetitive firing.

  • Carbamazepine:

    • Binds to voltage-dependent sodium channels in their inactive state, preventing they from re-opening, which limits high-frequency neuronal discharge.

  • Lamotrigine:

    • Specifically targets and inhibits voltage-sensitive sodium channels, leading to a reduction in the release of excitatory neurotransmitters like glutamate and aspartate. This is particularly effective for the depressive phases of bipolar disorder.

SIDE EFFECTS MANAGEMENT

  • Strategies for addressing common side effects and monitoring blood levels during anticonvulsant therapy.

SECOND-GENERATION ANTIPSYCHOTICS (SGAs)

  • Role as adjunctive therapy in bipolar disorder, potential benefits, and concerns regarding metabolic syndrome and other serious effects.

MECHANISM OF ACTION OF ANTIPSYCHOTICS

  • Dual Receptor Antagonism:

    • Most SGAs act as antagonists at dopamine D<em>2D<em>2 receptors and serotonin 5−HT</em>2A5-HT</em>{2A} receptors.

    • Antagonism at 5−HT2A5-HT_{2A} receptors can improve mood and reduce extrapyramidal side effects compared to first-generation antipsychotics.

  • Mood Stabilization:

    • Specific agents (e.g., Quetiapine) have active metabolites that inhibit norepinephrine reuptake, contributing to antidepressant effects.

COMBINATION THERAPIES

  • Patients often require multiple medications; careful monitoring for symptoms and adjustments necessary.

  • Specific recommendations for acute and ongoing treatment episodes, including consideration of antidepressants cautiously.

LENGTH OF TREATMENT

  • Long-term treatment and the importance of maintaining mood stabilizer therapy for positive outcomes.

PATIENT EDUCATION

  • Emphasis on compliance, symptom identification, and medication adherence.

  • Address models of psychotherapeutic approaches and therapist roles in patient stabilization.

KEY DISCUSSIONS

  • Possible challenges in treating clients presenting with bipolar disorder and creative solutions.

  • Discussions surrounding treatment for bipolar-related disorders.