Mood Disorders PDF

MOOD DISORDERS  Mood disorders encompass a range of mental health conditions where a primary symptom is a disturbance in mood. These disorders are characterized by periods of depression, mania, or both.  The two major types of mood disorders are Depressive Disorders (e...

MOOD DISORDERS  Mood disorders encompass a range of mental health conditions where a primary symptom is a disturbance in mood. These disorders are characterized by periods of depression, mania, or both.  The two major types of mood disorders are Depressive Disorders (e.g., Major Depressive Disorder) and Bipolar Disorders.  Bipolar disorders are characterized by significant mood fluctuations that range from periods of extreme elation (mania or hypomania) to severe depression. TYPES OF BIPOLAR DISORDERS  Bipolar I Disorder:  Defined by the occurrence of at least one manic episode that lasts for at least a week or requires hospitalization.  Manic episodes may be preceded or followed by major depressive episodes, though depressive episodes are not required for a Bipolar I diagnosis.  Manic episodes can severely impair functioning and may involve psychotic features. TYPES OF BIPOLAR DISORDERS  Bipolar II Disorder:  Characterized by the presence of hypomanic episodes (less severe than mania) and major depressive episodes.  Hypomania lasts for at least 4 days but does not cause the level of dysfunction seen in full- blown mania.  The depressive episodes in Bipolar II tend to be more chronic and debilitating than in Bipolar I. TYPES OF BIPOLAR DISORDERS  Cyclothymic Disorder:  A milder form of bipolar disorder involving numerous periods of hypomanic symptoms and depressive symptoms that do not meet the full criteria for a major depressive episode.  Symptoms persist for at least two years in adults (one year in children and adolescents) but are less intense than those in Bipolar I or II. TYPES OF BIPOLAR DISORDERS  Other Specified and Unspecified Bipolar and Related Disorders:  These categories apply when the full criteria for bipolar I or II are not met, but the person still experiences significant mood disturbances. SYMPTOMS OF BIPOLAR DISORDER---MANIA (SEEN IN BIPOLAR I)  Elevated or irritable mood  Increased energy, activity, or restlessness  Inflated self-esteem or grandiosity  Decreased need for sleep (feeling rested after only a few hours)  Pressured speech, talking rapidly and excessively SYMPTOMS OF BIPOLAR DISORDER---MANIA (SEEN IN BIPOLAR I)  Racing thoughts or flight of ideas  Impulsivity (engaging in high-risk activities such as reckless spending, gambling, or unsafe sex)  Poor judgment or decision-making  In extreme cases, delusions or hallucinations HYPOMANIA (SEEN IN BIPOLAR II AND CYCLOTHYMIA)  Similar to mania but less severe and shorter in duration  No significant impairment in social or occupational functioning  May still involve elevated mood, increased energy, and impulsivity, but typically without psychotic features DEPRESSIVE EPISODES (PRESENT IN BIPOLAR I, II, AND CYCLOTHYMIA):  Persistent sadness, hopelessness, or feelings of worthlessness  Loss of interest or pleasure in most activities (anhedonia)  Fatigue or loss of energy  Changes in appetite or weight (either increase or decrease)  Sleep disturbances (insomnia or hypersomnia)  Difficulty concentrating or making decisions  Suicidal thoughts or behaviors TREATMENT OF BIPOLAR DISORDER  Effective treatment of bipolar disorder requires a combination of pharmacological interventions, psychotherapy, and lifestyle modifications. The goal is to stabilize mood, prevent relapse, and help the patient lead a productive life. 1. PHARMACOLOGICAL TREATMENT  Mood Stabilizers  Antipsychotics  Antidepressants  Combination Therapy MOOD STABILIZERS  1. Lithium  2. Anticonvulsants (Used as Mood Stabilizers)  Valproate / Valproic Acid  Divalproex Sodium  Lamotrigine  Carbamazepine  3. Second-Generation Antipsychotics (Atypical Antipsychotics)  4. Benzodiazepines (Adjunctive Use in Acute Mania)  Clonazepam  Lorazepam) LITHIUM  Chemical Formula: Li  Class: Mood stabilizer  First Approved: 1970 (for mania treatment by FDA)Primary Use:  Bipolar disorder (BD) management – acute mania and long-term mood stabilization  Formulations: Lithium carbonate, Lithium citrate PHARMACOKINETICS---LITHIUM  Absorption:  Well absorbed orally, peak plasma concentration in 1-2 hours  Bioavailability: 80-100%  Food has little effect on absorption PHARMACOKINETICS---LITHIUM  Distribution:  Widely distributed in body water  Not bound to plasma proteins  Slow entry into intracellular compartments  Crosses the blood-brain barrier (BBB), though slowly PHARMACOKINETICS---LITHIUM  Metabolism:  Lithium is not metabolized by the liver  Excreted unchanged via the kidneys  Elimination:  Half-life: 18–36 hours (longer in elderly or those with renal impairment)  Excreted 95% in urine, minimal in sweat and feces  Narrow therapeutic window: 0.6–1.2 mEq/L LITHIUM---MOA  Lithium's mechanism is not fully understood but involves:  Modulation of neurotransmission:  Inhibits inositol monophosphatase → Reduces inositol triphosphate (IP3) signaling  Affects neurotransmitter pathways (dopamine, serotonin, glutamate, and GABA)  Neuroprotection & Synaptic Plasticity:  Promotes BDNF (brain-derived neurotrophic factor) expression  Stabilization of Mood:  Reduces manic episodes by decreasing abnormal brain excitability LITHIUM--------------CLINICAL USES  Bipolar Disorder  Acute Mania: Reduces symptoms such as agitation, grandiosity, and flight of ideas  Maintenance Therapy: Prevents manic and depressive relapses  Adjunctive Therapy in Unipolar Depression  Used with antidepressants when monotherapy is ineffective  Schizoaffective Disorder  Helps control mood swings when psychotic symptoms coexist  Cluster Headaches  Occasionally prescribed as a preventive agent LITHIUM  Dosing and Therapeutic Monitoring  Starting dose: 300 mg two or three times daily  Maintenance dose: 900–1200 mg/day (varies by response) LITHIUM------------ADVERSE EFFECTS  Common  Tremor, nausea, diarrhea  Polyuria and polydipsia (due to nephrogenic diabetes insipidus)  Weight gain  Cognitive effects (difficulty concentrating)  Severe/Chronic  Hypothyroidism  Renal impairment (reduced glomerular function over time)  Cardiac issues: Bradycardia, T-wave changes on ECG  Lithium toxicity LITHIUM------------- TOXICITY  Occurs when serum levels > 1.5 mEq/L  Mild toxicity: Tremors, confusion, nausea, diarrhea  Moderate to severe toxicity: Seizures, ataxia, altered mental status, coma  Treatment: Immediate cessation, IV fluids, dialysis if severe LITHIUM  Contraindications  Renal impairment (reduces lithium clearance)  Pregnancy (teratogenic risks, especially Ebstein’s anomaly)  Severe dehydration or sodium depletion LITHIUM  Pregnancy and Lactation  Pregnancy: Avoid unless benefits outweigh risks (Ebstein’s anomaly in 1st trimester)  Breastfeeding: Contraindicated, as lithium passes into breast milk LITHIUM  Lithium is a first-line mood stabilizer with well-established efficacy in bipolar disorder management. However, narrow therapeutic index,  Lithium remains a cornerstone treatment, particularly valued for reducing suicidal ideation and relapse prevention in bipolar patients. VALPROATE / VALPROIC ACID  Chemical Structure: Simple branched- chain carboxylic acid.  Forms:  Valproic Acid (Depakene) – Liquid or capsule.  Sodium Valproate – Sodium salt form.  Divalproex Sodium (Depakote) – Combination of sodium valproate and valproic acid for better GI tolerance.  Class: Anticonvulsant, mood stabilizer. PHARMACOKINETICS----VALPROATE / VALPROIC ACID  Absorption  Well absorbed orally; bioavailability ~100%.  Distribution  Highly protein-bound (~90%) to albumin.  Crosses the blood-brain barrier and the placenta.  Metabolism  Liver metabolism via glucuronidation and beta-oxidation.  Inhibits cytochrome P450 enzymes, potentially causing drug interactions.  Elimination  Half-life: 9–16 hours (longer with chronic use).  Excreted mainly in urine (as metabolites). VALPROATE / VALPROIC ACID ----- MOA  Inhibition of Voltage-Gated Sodium Channels  Prevents repetitive firing of neurons, stabilizing electrical activity.  Enhancement of GABAergic Activity  Modulation of Calcium Channels  Reduces T-type calcium currents, which are implicated in seizures and mood instability.  Gene Expression and Neuroprotection  Increases expression of brain-derived neurotrophic factor (BDNF). CLINICAL USES-----VALPROATE / VALPROIC ACID  Mood Disorders  Acute mania (bipolar disorder).  Maintenance therapy to prevent recurrence of manic episodes.  Sometimes used for bipolar depression in combination with other agents.  Epilepsy / Seizures  Generalized seizures (tonic-clonic, myoclonic, absence seizures).  Focal seizures.  Migraine Prophylaxis  Prevents chronic and episodic migraines.  Off-label Uses  Schizoaffective disorder.  Impulsivity and aggression (in neuropsychiatric disorders). VALPROATE / VALPROIC ACID---- SIDE EFFECTS  Common Side Effects  Nausea, vomiting, diarrhea.  Weight gain.  Tremor and sedation.  Hair thinning (reversible).  Serious Adverse Effects  Hepatotoxicity (risk highest in children under 2 years).  Pancreatitis (potentially fatal).  Hyperammonemia (can cause encephalopathy).  Thrombocytopenia (monitor platelets). VALPROATE / VALPROIC ACID---- SIDE EFFECTS  Neurotoxic Effects  Drowsiness, confusion, ataxia.  Rarely, can cause parkinsonism.  Reproductive Issues  Teratogenicity: High risk of neural tube defects (e.g., spina bifida).  Fetal valproate syndrome: Cognitive impairment, facial abnormalities.  Ovarian dysfunction: Risk of polycystic ovarian syndrome (PCOS). VALPROATE / VALPROIC ACID  Toxicity and Overdose  Symptoms: Confusion, vomiting, drowsiness, hypotension, respiratory depression, seizures, and coma.  Treatment:  Supportive care (airway protection, IV fluids).  L-carnitine for hyperammonemia.  Hemodialysis in severe cases. VALPROATE / VALPROIC ACID  Valproate is a versatile mood stabilizer and anticonvulsant.  It is widely used in the treatment of bipolar disorder, epilepsy, and migraines. However, due to its teratogenicity, hepatotoxicity, and drug interactions,  It remains a valuable option, especially for patients with acute mania and rapid- cycling bipolar disorder. CARBAMAZEPINE  Carbamazepine (CBZ) is an anticonvulsant and mood-stabilizing drug, widely used to treat epilepsy, bipolar disorder, and certain chronic pain conditions such as trigeminal neuralgia.  It was one of the first anticonvulsants to be used as a mood stabilizer after lithium, particularly in the treatment of bipolar disorder. CARBAMAZEPINE-------MOA  The exact mechanism by which carbamazepine acts as a mood stabilizer is still not fully understood.  Sodium Channel Blockade  CBZ inhibits voltage-gated sodium channels, stabilizing hyperexcitable nerve membranes. This reduces the excessive firing of neurons that might contribute to manic episodes.  Enhancement of GABAergic Activity  It indirectly enhances the effects of gamma- aminobutyric acid (GABA), an inhibitory neurotransmitter, which helps counter hyperactivity in the brain. CARBAMAZEPINE-------MOA  Reduction of Glutamate Transmission  By modulating glutamate release, carbamazepine reduces excitatory neurotransmission, which might prevent mania or reduce its intensity.  Effects on Calcium and Serotonin Pathways  CBZ can influence calcium ion channels and modulate serotonergic pathways, both of which are involved in mood regulation. CARBAMAZEPINE------------THERAPEUTIC USES  Carbamazepine is primarily used in the management of bipolar disorder,  Particularly in patients with manic, mixed, or rapid-cycling episodes,  In cases where patients do not respond to lithium or other medications. CARBAMAZEPINE-----------THERAPEUTIC USES  Bipolar Disorder  Acute Mania: CBZ is effective in controlling acute manic episodes and reducing irritability, euphoria, and impulsivity.  Prophylaxis: It helps prevent recurrent manic or depressive episodes, though it may be more effective in preventing mania than depression.  Rapid-Cycling Bipolar Disorder: CBZ is an alternative treatment for patients who experience rapid shifts between mania and depression. CARBAMAZEPINE---------------THERAPEUTIC USES  2. Bipolar Depression (Limited Efficacy)  Though CBZ helps prevent depressive episodes, it is generally less effective than lithium or lamotrigine in treating acute bipolar depression. CARBAMAZEPINE----- PHARMACOKINETICS  Absorption: CBZ is well absorbed orally, though it has a slow onset of action, taking 1–2 weeks to reach therapeutic levels.  Metabolism: It is metabolized in the liver by CYP3A4 enzymes into an active metabolite, carbamazepine-10,11-epoxide.  Autoinduction: CBZ induces its own metabolism over time, leading to decreasing plasma levels, which can complicate dosing.  Half-life: Initially 25–65 hours but reduces to 12–17 hours due to autoinduction. CARBAMAZEPINE------ADVERSE EFFECTS  Common Side Effects  Dizziness, drowsiness, headache, blurred vision, and nausea.  Hyponatremia (low sodium levels) due to SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion). CARBAMAZEPINE-----ADVERSE EFFECTS  Agranulocytosis and aplastic anemia: Rare but life-threatening hematologic conditions.Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis CARBAMAZEPINE  Serious Side Effects  Agranulocytosis and aplastic anemia: Rare but life-threatening hematologic conditions.  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis ADVANTAGES OF CARBAMAZEPINE IN MOOD STABILIZATION  Effective in lithium-resistant patients.  Useful in mixed and rapid-cycling bipolar disorder.  Fewer weight gain and cognitive issues compared to other mood stabilizers like valproate or atypical antipsychotics. CARBAMAZEPINE----LIMITATIONS AND CONSIDERATIONS  Delayed Onset of Action: It may take 1–2 weeks for clinical effects to become evident.  Autoinduction of Metabolism: Requires close monitoring of plasma levels.  Limited Efficacy in Bipolar Depression: Not the first-line drug for depressive episodes.  Teratogenic Effects: Can cause fetal abnormalities (e.g., neural tube defects) and is usually avoided in pregnancy unless no alternatives are available.