Mood Stabilizers: Effective Treatment for Mania and Bipolar Disorder
Mood stabilizers are a class of drugs used to treat bipolar disorder, a mental health condition characterised by episodes of mania (elevated, irritable mood), depression, and sometimes psychosis. These medications work by balancing the levels of certain neurotransmitters in the brain, particularly dopamine, serotonin, and norepinephrine. The goal of treatment with mood stabilizers is to prevent or reduce the frequency and severity of bipolar episodes, as well as to stabilize mood and improve the overall quality of life.
The following table provides an overview of some commonly used mood stabilizers:
|Drug Name||Mechanism of Action||Indications||Adverse Effects||Contraindications|
Modulation of neurotransmitter signaling: inhibits phosphoinositol signaling and alters intracellular calcium concentration
|Bipolar disorder, mania, depression, suicidal behavior||Weight gain, hand tremors, increased thirst and urination, nausea, vomiting, diarrhea, kidney and thyroid problems, lithium toxicity||Severe renal or cardiovascular disease, dehydration, sodium depletion, pregnancy and breastfeeding|
Inhibition of GABA transaminase: increases GABA concentration, and HDAC inhibition: epigenetic modulation of gene expression
|Bipolar disorder, mania, seizure disorders||Nausea, vomiting, dizziness, hair loss, tremors, weight gain, liver toxicity, pancreatitis, suicidal behavior, birth defects in pregnancy||Liver disease, pancreatitis, mitochondrial disorders, pregnancy and breastfeeding|
Inhibition of voltage-gated sodium channels: reduces neuronal firing and hyperexcitability
|Bipolar disorder, mania, seizure disorders, trigeminal neuralgia||Dizziness, drowsiness, nausea, vomiting, skin rash, low sodium levels, liver toxicity, suicidal behavior, birth defects in pregnancy||Bone marrow suppression, liver disease, pregnancy and breastfeeding|
|Lamotrigine||Inhibition of voltage-gated sodium channels: reduces neuronal firing and hyperexcitability||Bipolar disorder, depression||Headaches, dizziness, double vision, skin rash, suicidal behavior, birth defects in pregnancy||Stevens-Johnson syndrome, liver disease, pregnancy and breastfeeding|
|Inhibition of voltage-gated sodium channels: reduces neuronal firing and hyperexcitability||Bipolar disorder, mania, seizure disorders||Nausea, vomiting, dizziness, drowsiness, skin rash, low sodium levels, liver toxicity, suicidal behavior, birth defects in pregnancy||Hypersensitivity to carbamazepine, hyponatremia, pregnancy and breastfeeding|
|Topiramate||Modulation of GABA and glutamate signaling||Bipolar disorder, seizure disorders, weight loss||Dizziness, drowsiness, confusion, memory problems, suicidal behavior, kidney stones, birth defects in pregnancy, glaucoma, metabolic acidosis, heat intolerance||
|Divalproex sodium||Inhibition of GABA transaminase: increases GABA concentration, and HDAC inhibition: epigenetic modulation of gene expression||
Bipolar disorder, mania, seizure disorders
|Nausea, vomiting, dizziness, hair loss, tremors, weight gain, liver toxicity, pancreatitis, suicidal behavior, birth defects in pregnancy||Liver disease, pancreatitis, mitochondrial disorders, pregnancy and breastfeeding|
In addition to the drugs listed in the table, other medications may also be used as mood stabilizers, including antipsychotics and antidepressants. However, these drugs are typically used in combination with other mood stabilizers or under careful monitoring, as they can also have significant adverse effects.
Lithium is often considered the first-line treatment for bipolar disorder, particularly for acute mania episodes. Though it is effective in controlling acute mania, the response is slow and control of plasma levels is difficult during the acute phase.
Oral valproate in a relatively high dose is considered a first-line treatment option for mania. It acts faster than lithium but slower than antipsychotics with or without a benzodiazepine. Valproate also has a more favorable safety profile compared to lithium.
Divalproex, which is a compound of valproic acid, is often preferred due to its better tolerance in the stomach. When combined with an atypical antipsychotic, valproate has a high success rate in managing acute mania.
Carbamazepine and oxcarbazepine are anticonvulsant drugs that also have mood-stabilizing properties. Their mechanism of action involves inhibiting voltage-gated sodium channels, reducing neuronal firing and hyperexcitability. Carbamazepine is effective in treating bipolar disorder, mania, seizure disorders, and trigeminal neuralgia.
Oxcarbazepine has similar adverse effects, but it may be better tolerated in some individuals who have had adverse reactions to carbamazepine.
Lamotrigine is another anticonvulsant drug that is used primarily for the maintenance treatment of bipolar disorder and depression. Its mechanism of action involves inhibiting voltage-gated sodium channels, reducing neuronal firing and hyperexcitability. Lamotrigine can cause side effects such as headaches, dizziness, double vision, and skin rash, including a rare but serious condition called Stevens-Johnson syndrome. It is also contraindicated in individuals with liver disease or who are pregnant or breastfeeding.
Gabapentin and topiramate are two other anticonvulsant drugs that have been used as mood stabilizers. Gabapentin increases GABA concentrations and modulates calcium channels, while topiramate modulates both GABA and glutamate signaling. Gabapentin can cause side effects such as dizziness, drowsiness, weight gain, and liver toxicity, while topiramate can cause side effects such as dizziness, drowsiness, confusion, memory problems, and kidney stones.
- Lithium is a small monovalent cation, established as the standard antimanic and mood-stabilizing drug.
- Lithium is used to suppress mania and exert a prophylactic effect in bipolar disorder.
- Lithium has no acute effects in normal individuals or in bipolar patients.
- Lithium acts as a mood stabilizer in bipolar disorder and gradually suppresses acute mania episodes.
The mechanism of the antimanic and mood-stabilizing action of lithium is not known, but several hypotheses have been proposed.
- Lithium inhibits the action of ADH on distal tubules in the kidney and causes a diabetes insipidus-like state.
- It has an insulin-like action on glucose metabolism.
- It inhibits the release of thyroid hormones, and a majority of treated patients remain in a state of compensated euthyroidism.
- It is well absorbed orally, is neither protein-bound nor metabolized, and distributes in extracellular water.
- Lithium is handled by the kidney in much the same way as Na+ and is reabsorbed in the proximal convoluted tubule.
- Monitoring of serum lithium concentration is essential for optimizing therapy; 0.5–0.8 mEq/L is considered optimum for maintenance therapy in bipolar disorder.
- Side effects are common but mostly tolerable, and toxicity occurs at levels only marginally higher than therapeutic levels.
- Alternatives to lithium include anticonvulsants and atypical antipsychotics.
- Sodium valproate is a first-line treatment for mania and is also an effective prophylactic in bipolar disorder.
- Carbamazepine controls mania and prolongs remission in bipolar disorder but is less effective than lithium or valproate in acute mania.
- Lamotrigine is effective for prophylaxis of depression in bipolar disorder and is used in maintenance therapy of type II bipolar disorder.
- Atypical antipsychotics such as olanzapine, risperidone, aripiprazole, and quetiapine are now the first-line drugs for controlling acute mania.
- Aripiprazole has recently emerged as the favored drug for treating mania in bipolar I disorder, both as monotherapy and adjuvant to lithium or valproate.
- Strong evidence of the efficacy of quetiapine has emerged in bipolar depression.
- Combination therapy with an atypical antipsychotic and lithium or valproate has demonstrated high efficacy in acute phases as well as for maintenance therapy of bipolar disorder.
|Mechanism of Action||Effects|
|CNS||Lithium acts as a mood stabilizer in bipolar disorder and gradually suppresses acute mania episodes.|
|Other Actions||Lithium inhibits the action of ADH on distal tubules in the kidney and causes a diabetes insipidus-like state. It also has an insulin-like action on glucose metabolism and inhibits the release of thyroid hormones.|
|Pharmacokinetics||Control of Therapy|
|Lithium is well absorbed orally, is neither protein-bound nor metabolized, and distributes in extracellular water.||Monitoring of serum lithium concentration is essential for optimizing therapy; 0.5–0.8 mEq/L is considered optimum for maintenance therapy in bipolar disorder.|
|Alternatives to Lithium||Effects|
|Sodium Valproate||First-line treatment for mania is also an effective prophylactic in bipolar disorder.|
|Carbamazepine||Controls mania and prolongs remission in bipolar disorder but is less effective|
- Acute intoxication is characterized by vomiting, diarrhea, coarse tremors (fine tremors in mild intoxication), ataxia, coma, and convulsions.
- More serious effects involve mental confusion, hyperreflexia, dysarthria, seizures, and cranial and focal neurological signs progressing to coma and death.
- Other toxic effects are cardiac arrhythmias, hypotension, and albuminuria.
- There is no specific antidote for lithium. Dialysis is the most effective means of removing Li from the body. It is indicated at serum Li levels of > 4 mEq/L in acute overdose or > 1.5 mEq/L in chronic overdose.
Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.