MODE OF ACTION

Mood stabilizers represent a class of psychiatric drugs central to the treatment of bipolar disorder, and also beneficial for other conditions featuring mood instability. The precise mechanisms through which mood stabilizers exert their effects are complex and still being investigated. Several prominent theories attempt to elucidate their workings:

• Neurotransmitter Regulation: One prevailing hypothesis suggests that mood stabilizers function by adjusting the levels of key neurotransmitters within the brain. These neurotransmitters, notably serotonin, dopamine, and norepinephrine, are critical in mood regulation. Imbalances in these neurochemicals are thought to contribute to mood swings and instability. Mood stabilizers may help restore equilibrium, thereby mitigating the symptoms of bipolar and related mood disorders.

• Ion Channel Modulation: Another theory centers on the idea that mood stabilizers influence the activity of specific ion channels in the brain, particularly those governing the flow of sodium and calcium ions. These channels are vital for controlling neuronal excitability. Dysregulation of ion channel activity is implicated in the mood fluctuations seen in bipolar disorder. Mood stabilizers may work to normalize the function of these ion channels, which can reduce the severity of mood swings.

• Brain Region Influence: A third perspective proposes that mood stabilizers impact the structure and function of brain regions crucial for mood regulation, such as the prefrontal cortex and the amygdala. These areas are thought to be fundamental in emotional processing and response. Structural or functional abnormalities in these regions can contribute to mood instability. Mood stabilizers may aid in normalizing the structure and activity within these brain regions, thus alleviating mood disorder symptoms.

Pharmacodynamics of Mood Stabilizers

Mood stabilizers can exert a range of pharmacodynamic effects, influencing various bodily systems:

1. Cardiovascular Effects: Certain mood stabilizers, for example, lithium, can impact the cardiovascular system, potentially causing alterations in heart rate and blood pressure. Regular cardiovascular monitoring is often recommended for patients on these medications.

2. Electrolyte Imbalance: Some mood stabilizers, such as lithium, can disrupt the body’s electrolyte balance, particularly affecting sodium and potassium levels. This can manifest as side effects like nausea, vomiting, diarrhea, and muscle weakness. In the context of mania, reducing cerebral sodium concentration is thought to contribute to symptom control by diminishing neuronal excitability.

3. Renal Function Changes: Lithium is primarily eliminated from the body by the kidneys. Long-term lithium use can, in some cases, lead to kidney damage or impairment. Regular kidney function tests are therefore often necessary for individuals undergoing lithium therapy.

4. Thyroid Function Alterations: Certain mood stabilizers, including lithium and valproic acid, can affect thyroid function, potentially leading to hypothyroidism (underactive thyroid). Symptoms of hypothyroidism can include fatigue, weight gain, and cold intolerance.

5. Hepatic Function Effects: Some mood stabilizers, such as valproic acid, can influence liver function, potentially causing elevations in liver enzymes. Regular liver function tests may be indicated for patients taking valproic acid.

6. Metabolic Changes: Medications like valproic acid can affect metabolism, potentially resulting in weight gain as a side effect.

LITHIUM CARBONATE (ESKALITH)

Lithium carbonate is a widely prescribed medication classified as a mood stabilizer, primarily used in the treatment of bipolar disorder. It is a naturally occurring element present in trace amounts in the body. Its therapeutic mechanism involves modulating the levels of specific neurotransmitters in the brain, particularly serotonin and norepinephrine.

Indications of Lithium Carbonate

Clinical applications for lithium carbonate include:

• Bipolar Affective Disorder: Effective in managing bipolar disorder characterized by mood swings.

• Prophylaxis in Bipolar Disorder: Used as a preventative measure to extend the intervals between mood episodes.

• Aggressive Disorders: May be utilized in managing aggression associated with personality disorders.

• Schizoaffective Disorder: Can be used in the treatment of schizoaffective disorder.

• Alcoholism: Sometimes used in the management of alcoholism.

Contraindications of Lithium Carbonate

Situations where lithium carbonate is generally avoided include:

• Hypersensitivity: Individuals with a known allergy to lithium carbonate or any of its formulation components should not use this medication.

• Renal Impairment: Lithium elimination relies heavily on kidney function. Patients with kidney disease are at increased risk of lithium toxicity. Lithium is contraindicated in severe kidney disease or end-stage renal disease.

• Dehydration: Lithium can affect electrolyte balance, particularly sodium. Dehydration can elevate the risk of lithium toxicity. Individuals who are dehydrated or prone to dehydration should avoid lithium.

• Cardiovascular Conditions: Lithium can affect the cardiovascular system. Patients with a history of heart disease or cardiovascular conditions may have a higher risk of complications with lithium.

• Pregnancy and Breastfeeding: Lithium can cross the placenta and enter breast milk, potentially harming a developing fetus or nursing infant. It is generally contraindicated during pregnancy and breastfeeding, unless the potential benefits are deemed to outweigh the risks.

• Hyponatremia: Lithium can induce or worsen hyponatremia (low sodium levels), a potentially life-threatening condition. Lithium is contraindicated in severe or uncontrolled hyponatremia.

• Seizure Disorders: Lithium can lower the seizure threshold. It is contraindicated in individuals with a history of seizures or epilepsy.

• Thyroid Dysfunction: Lithium can impact thyroid function and may exacerbate hypothyroidism (underactive thyroid). It is contraindicated in severe hypothyroidism.

Dosage

Dosage guidelines for lithium carbonate vary based on age and condition:

• Adult Dosage:

  • Initial Dose: Typically starts at 300-600 mg daily, divided into two or three administrations.

  • Dosage Titration: Gradually increased, typically by 300-600 mg weekly, until a therapeutic blood level is reached.

  • Maintenance Dose: Can range from 600-2400 mg per day, adjusted to individual needs and therapeutic blood levels.

• Pediatric Dosage:

  • Lithium carbonate is generally not prescribed for children under 12 due to limited safety and efficacy data in this age group.

  • Adolescents (12-18 years): Starting dose is typically 300 mg daily, divided into two or three doses. Dosage is gradually increased by 150-300 mg weekly as needed until therapeutic levels are achieved.

Routine Investigations

Note: Prior to initiating lithium carbonate therapy, baseline investigations are essential:

1. Blood Serum Lithium Level:

   • Normal Range (prophylactic): 0.6-1.2 mEq/L (for relapse prevention in Bipolar Affective Disorder – BAD).

   • Therapeutic Range (acute mania): 0.8-1.2 mEq/L (for treating acute mania).

   • Toxic Levels: Above 2.0 mEq/L.

Additional Investigations:

1. Blood Tests:

   • Complete Blood Count (CBC): To assess overall health.

   • Blood Chemistry Panel: Includes electrolytes (sodium, potassium), kidney function tests, liver function tests, and thyroid function tests.

2. Urinalysis: To assess kidney function and detect potential kidney damage.

3. Electrocardiogram (ECG): To evaluate heart function and identify pre-existing cardiac conditions.

4. Pregnancy Test: For women of childbearing potential, to rule out pregnancy before starting lithium.

5. Medical History: Comprehensive assessment of past and current medical conditions, medications, and allergies.

6. Psychiatric Evaluation: Thorough assessment of symptoms and diagnosis of bipolar disorder.

7. Baseline Mood Assessment: To establish a baseline for monitoring medication effects on mood and behavior.

N.B: Patients on lithium carbonate may also be prescribed thyroxine (levothyroxine) to counter potential hypothyroidism, as lithium can interfere with thyroid gland function.

Side effects:

Lithium carbonate is typically well-tolerated when used as a mood stabilizer. However, like all medications, it can produce both short-term and long-term side effects.

Short-Term Side Effects:

• Gastrointestinal disturbances: Nausea, vomiting, and diarrhea

• Oral dryness and increased thirst: Dry mouth and thirst

• Frequent urination: Increased urination

• Muscular weakness and involuntary trembling: Muscle weakness and tremors

• Tiredness and sleepiness: Fatigue and drowsiness

• Cephalalgia: Headaches

• Increased appetite and weight gain: Increased appetite and weight gain

• Mild cognitive difficulties: Mild cognitive impairment (attention, memory, or problem-solving)

• Skin reactions: Skin rash or acne

• Giddiness: Vertigo

• Speech difficulties: Dysarthria

• Heart rhythm irregularities: Cardiac arrhythmias

• Swelling: Oedema in some patients

• Involuntary eye movements: Nystagmus

Many of these short-term side effects are generally mild and often diminish as the body adapts to the medication. Adjusting dosage or timing of medication, or taking it with food, can sometimes help manage these effects.

Long-Term Side Effects:

• Kidney damage or failure: Kidney damage or kidney failure

• Underactive thyroid gland: Hypothyroidism

• Increased diabetes risk: Increased risk of diabetes mellitus

• Heart disease risk: Cardiovascular disease

• Neurological symptoms: Neurological effects (hand tremors, slurred speech, impaired coordination)

• Birth defects: Teratogenicity (in fetuses exposed during pregnancy)

• Reduced thyroid hormone levels: Hypothyroidism (due to lithium interference with metabolism)

• Kidney-related diabetes insipidus: Nephrogenic diabetes insipidus

• Calcium depletion from bones: Depletion of calcium in bones

• Memory problems: Memory impairment

NB: Combining high doses of neuroleptics like haloperidol with long-term lithium use may, in rare cases, lead to irreversible toxic encephalopathy.

Management of lithium toxicity

General principles for managing lithium toxicity include:

1. Lithium Discontinuation: Immediately stop lithium intake to prevent further toxicity.

2. Fluid and Electrolyte Restoration: Administer intravenous fluids to flush out excess lithium and restore electrolyte balance.

3. Supportive Care: Hospitalization for close monitoring of vital signs and mental status may be required. In severe cases, mechanical ventilation and dialysis might be necessary.

4. Pharmacological Symptom Management: Medications may be used to manage specific symptoms such as nausea, vomiting, seizures, or agitation.

5. Immediate Assessment: Evaluate serum lithium levels, electrolytes, renal function, and ECG promptly.

6. Fluid and Electrolyte Balance: Maintain fluid and electrolyte balance.

7. Hemodialysis: In cases of serious lithium toxicity, hemodialysis should be considered.

8. Gastric Decontamination: For recent lithium ingestion, gastric lavage or induction of emesis followed by activated charcoal may be used to remove residual gastric content.

9. Fluid Intake: Encourage the patient to drink fluids if possible.

NURSE’S RESPONSIBILITIES FOR PATIENT RECEIVING LITHIUM

Nurses play a vital role in ensuring safe and effective lithium therapy:

1. Comprehensive Assessment: Conduct a thorough pre-lithium assessment, including physical examination, medical history, and baseline laboratory tests. Regularly monitor for potential side effects or adverse reactions.

2. Patient and Family Education: Educate patients and families about proper lithium use, including dosage, timing, potential side effects, and the importance of maintaining consistent sodium intake and avoiding dehydration.

3. Medication Administration: Administer lithium carbonate as prescribed, monitor medication adherence, and report any missed doses or concerns.

4. Ongoing Monitoring: Regularly monitor for side effects, adverse reactions (tremors, confusion, kidney dysfunction), and lithium blood levels, electrolytes, and kidney function. Report any abnormalities to the healthcare provider.

5. Interdisciplinary Collaboration: Collaborate with the healthcare team to ensure safe and effective lithium use. Communicate any patient condition changes or concerns promptly.

6. Pre-Lithium Workup: Ensure completion of a pre-lithium workup, including physical history, ECG, blood studies (FBS, creatinine, electrolytes), and urinalysis. Assess renal and thyroid function due to potential lithium-related side effects.

Precautions

To maximize therapeutic benefits and minimize lithium toxicity risk:

• Regular Dosing: Lithium must be taken consistently, preferably at the same time each day. If a dose is missed, the patient should wait for the next scheduled dose and avoid doubling doses.

• Initial Side Effects: Mild initial side effects (fine tremors, increased thirst/urination, nausea, anorexia) may occur as the body adjusts.

• Serious Side Effects: Serious side effects requiring immediate medical attention and potential lithium discontinuation include vomiting, severe tremors, sedation, muscle weakness, and vertigo.

• Hydration: Advise patients to maintain adequate hydration, especially to compensate for polyuria and prevent dehydration-related lithium toxicity.

• Dosage Adjustments: Be aware that factors such as new medications, dietary changes, or illnesses with fever/sweating can necessitate lithium dosage adjustments. Heavy physical labor and excessive sweating can lead to sodium loss, increasing lithium toxicity risk. Advise increased fluid and salt intake in such situations.

• Regular Serum Lithium Level Monitoring: Frequent monitoring of serum lithium levels is crucial. Blood samples should be drawn in the morning, 12-14 hours after the last dose.

• Follow-up Care: Emphasize the importance of regular follow-up appointments. Periodic blood tests (electrolytes, urea, creatinine, full blood count, thyroid function) should be conducted every six months.

SODIUM VALPROATE (EPILIM)

Sodium valproate is a medication used to manage a variety of neurological and psychiatric conditions. It belongs to the anticonvulsant drug class, typically used for epilepsy, but also effective for bipolar disorder, migraine prevention, and certain seizure types.

Mode of action

Sodium valproate’s mechanism involves increasing levels of gamma-aminobutyric acid (GABA), a neurotransmitter in the brain that calms overactive neurons and prevents seizures. It also has mood-stabilizing properties beneficial in treating bipolar disorder.

Dosage

Dosage varies depending on the condition and patient group:

• For Epilepsy:

  • Adults: Starting dose is 600-1000 mg daily, divided into two or three doses. Maintenance dose can be increased to 2500-3000 mg daily as needed.

  • Children: Starting dose is 10-15 mg/kg/day, divided into two or three doses. Maintenance dose can be increased to 30-60 mg/kg/day.

  • Elderly: Starting dose is lower, 250-500 mg daily, divided into two or three doses. Maintenance dose can be increased to 2000 mg daily.

• For Bipolar Disorder:

  • Adults: Starting dose is 500-750 mg daily, divided into two or three doses. Maintenance dose can be increased to 2000-2500 mg daily.

  • Children: Starting dose is 10-15 mg/kg/day, divided into two or three doses. Maintenance dose can be increased to 60 mg/kg/day.

  • Elderly: Starting dose is lower, 250-500 mg daily, divided into two or three doses. Maintenance dose can be increased to 2000 mg daily.

Indications of Sodium Valproate

Clinical uses of sodium valproate include:

1. Epilepsy: Prevention and control of seizures in various epilepsy types (generalized, partial, absence, myoclonic).

2. Bipolar Disorder: Mood stabilizer in bipolar disorder treatment.

3. Migraine Prophylaxis: Prevention of migraines, especially in patients unresponsive to other treatments or with frequent, severe migraines.

4. Neuropathic Pain: Treatment of neuropathic pain types like trigeminal neuralgia and diabetic neuropathy.

5. Agitation and Aggression: Management of agitation and aggression in dementia, autism, or other psychiatric conditions.

6. Alcohol Withdrawal: Management of alcohol withdrawal symptoms (seizures, delirium tremens).

Side effects

Common side effects of sodium valproate:

• Gastrointestinal effects: Nausea, vomiting, diarrhea, abdominal pain.

• Weight gain: Can cause weight gain and appetite changes.

• Sedation and drowsiness: May cause sedation and drowsiness, impairing operation of machinery or driving.

• Tremor: Involuntary movements of hands, arms, or other body parts.

• Hair loss: Usually reversible hair loss.

• Liver toxicity: Potential liver toxicity, especially in those with pre-existing liver issues or taking other liver-affecting medications.

• Blood disorders: Can affect blood cells, leading to anemia, low platelet counts, and bleeding risk.

• Pancreatitis: Rare but serious inflammation of the pancreas.

Contraindication

Situations to avoid or use sodium valproate with caution:

• Hypersensitivity: Allergy to sodium valproate.

• Liver disease: Risk of liver toxicity, use cautiously or avoid in pre-existing liver disease or abnormal liver function tests.

• Pancreatitis: History of pancreatitis.

• Pregnancy: Potential birth defects and developmental problems in fetuses. Avoid in pregnancy unless benefits outweigh risks.

• Breastfeeding: Passes into breast milk and may harm nursing infants. Avoid in breastfeeding women unless benefits outweigh risks.

• Urea cycle disorders: Can cause hyperammonemia in patients with urea cycle disorders.

Carbamazepine (tegretol)

Carbamazepine is primarily used to treat seizures and nerve pain, such as trigeminal neuralgia. It reduces excessive brain electrical activity causing seizures and decreases nerve fiber sensitivity to relieve pain. It is an anticonvulsant medication also used for bipolar and mood disorders.

Indications:

Clinical uses of carbamazepine include:

• Epilepsy: Especially complex partial seizures (drug of choice).

• Rapid Cycling Bipolar Disorder

• Acute Mania

• Trigeminal Neuralgia: Inflammation of the trigeminal nerve.

• Herpes Zoster (Shingles)

• Schizoaffective Disorder

Dosage

Dosage varies by age and condition:

1. Children: Starting dose for epilepsy is 10-20 mg/kg/day, divided into two or three doses, maximum 1000 mg/day. For trigeminal neuralgia, starting dose is 100 mg/day, divided into two doses, gradually increased as needed.

2. Adults: Starting dose for epilepsy is 200-400 mg/day, divided into two or three doses, maximum 1200 mg/day. For trigeminal neuralgia, starting dose is 100-200 mg/day, divided into two doses, gradually increased as needed.

3. Elderly: Starting dose may be lower than for younger adults, carefully monitored and adjusted.

Contraindications:

Situations where carbamazepine is contraindicated:

• Hypersensitivity: Allergy to carbamazepine.

• Bone marrow suppression: Can cause bone marrow suppression; avoid in patients with bone marrow suppression or blood disorders.

• History of agranulocytosis: History of agranulocytosis (severe white blood cell decrease).

• MAO Inhibitor Use: Do not use with monoamine oxidase (MAO) inhibitors due to potential life-threatening interactions.

• Pregnancy: Use with caution or avoid during pregnancy due to potential fetal harm.

• Breastfeeding: Consult healthcare provider before using while breastfeeding as it can be present in breast milk.

Side effects:

Common side effects of carbamazepine:

1. Dizziness or drowsiness

2. Nausea or vomiting

3. Headache

4. Blurred vision or double vision

5. Skin rash or itching

6. Dry mouth

7. Constipation or diarrhea

8. Swelling or fluid retention

9. Unsteadiness or loss of coordination

10. Fatigue or weakness

Adverse Effects

More serious adverse effects requiring medical attention:

1. Severe skin reactions: Stevens-Johnson syndrome or toxic epidermal necrolysis.

2. Blood disorders: Agranulocytosis or aplastic anemia.

3. Liver damage or hepatitis

4. Allergic reactions: Anaphylaxis.

5. Increased suicidal thoughts or behaviors: Especially in young adults.

6. Drug interactions: Can reduce effectiveness of birth control pills.