Mood stabilizer - BioPharma Notes

What are Mood Stabilizer?

Mood stabilizers are drugs that improve either depression or mania in bipolar disorder and doesn’t worsen or precipitate either state. In manic episodes, person feels highly energized and spirited. In depressive episodes, person feels very sad and lack of energy and motivation.
Bipolar disorder is a serious mental illness affecting about 2-5 % of the total population. It can initiate in early childhood or as late as in the 40s and 50s.
Some mood stabilizers are more effective at treating manic episodes and some are more effective for treating depressive episodes.

Mood stabilizers can be classified into two types; First generation and second-generation mood stabilizers.
First generation mood stabilizers were developed in 1960s and include lithium, carbamazepine and valproate.
Second generation mood stabilizers were developed in 1990s and include atypical antipsychotic drugs like olanzapine, clozapine, quetiapine, risperidone etc. Lamotrigine is also example of second-generation mood stabilizers.

The therapeutic use of lithium salt in psychosis was discovered by John Cade in 1949. Since then, it had been one of the widely prescribed medicine for bipolar disorder. It primarily helps to reduce mania but also helps to improve depression.
According to a study finding published in World Psychiatry, lithium was more effective than other mood stabilizers in treating bipolar disorder, it also reduces need of taking other supplemental medicines for bipolar disorder and reduce risk of suicide.
Its exact mechanism of action is not clear. It is believed to be associated with modification of GABA (Gamma Amin Butyric Acid) concentration in brain, alteration in release of neurotransmitters and hormones and decrease in synthesis of dopamine and noradrenaline in brain.
Lamotrigine is not sufficient in treating mixed episodes and severe mania. It reduces relapse of both manic and depressive episodes but doesn’t eliminate it.
Side effects of lithium therapy includes nausea, diarrhea, vomiting, weight gain, extrapyramidal symptoms (in patients taking antipsychotic drugs), cerebral ataxia, hypothyroidism (rare). It should be administered with care in patients with renal, cardiovascular or brain damage. It is also embryotoxic.
Due to its toxicity, it should only be prescribed by specialists who will also be responsible for monitoring it.

It is the first anticonvulsant used in bipolar disorder, both in acute mania and maintenance therapy since early 1970s.
Due to undesirable side effects and narrow therapeutic index of lithium, it may not be ideal option for all patients. in such cases, carbamazepine can be used as monotherapy. It can also be used in combination therapy along with lithium or other mood stabilizers.
carbamazepine is more effective in manic episodes than depressive episodes.
It is well tolerated on long term use. Most common side effects are dizziness, fatigue, somnolence. Some occasional serious side effects are agranulocytosis, aplastic anemia, Steven-Johnson syndrome.

Valproic acid is a broad-spectrum antiepileptic drug used in petitmal seizures, myoclonic epilepsy and focal epilepsy.
It is used in patients with mania who don’t respond to lithium or carbamazepine. It can be used as monotherapy or as combination therapy with other mood stabilizers.
Valproic acid is also useful in prophylaxis of bipolar disorder. It is effective as maintenance therapy to prevent relapse of bipolar disorder: more effective in preventing depressive relapses than manic relapses.
It is generally well tolerated. However, side effects like vomiting, tremor, ataxia, weight gain, hair loss, acute liver damage may occur. In patients with history of liver disease, liver function test should be performed before starting treatment and should be monitored on regular basis.

Atypical antipsychotics are found to be effective in treatment of acute mania in bipolar disorder, either as monotherapy or adjunctive treatment.
They are considered as 2^nd or 3^rd line therapy for treating bipolar depression.
More detailed research is required to study their effectiveness in bipolar disorder.

It is an established anticonvulsant drug approved for treatment of generalized and partial seizures and focal epilepsies. It was approved for its use as mood stabilizer in 1994.
Lamotrigine monotherapy is used to control the depressive symptoms in bipolar disorder. It can also be used in combination with lithium or valproic acid.
The mechanism by which lamotrigine acts as mood stabilizer is not exactly known.
Though, it is well tolerated side effects like rashes may occur. Rare chances of Steven Johnson syndrome are there.

Combination mood stabilizer therapy has become common in treatment of bipolar disorder.
Several combination of mood stabilizers is found to be effective. Most useful combination for mood stabilizing is the mixture of lithium and anticonvulsants.
The combination of lithium and valproate is a safe and effective regimen and is well tolerated. The current use of lithium and carbamazepine is also common. Lithium and carbamazepine may act synergistically.
Combination of lithium with antipsychotics like clozapine is effective but it can cause neurologic symptoms.
The combination of clozapine and carbamazepine is generally contraindicated because of their hematologic side effects. There is also a reported case of neuroleptic malignant syndrome.
There is lack of data regarding combination uses of some mood stabilizers like carbamazepine and lamotrigine, valproate and risperidone.
Thus, while prescribing combination therapy for bipolar disorder, proper attention should be given to maintain balance between reducing symptoms of bipolar disorder without causing unwanted side effects.

https://www.medicalnewstoday.com/articles/325214#summary
Chen C, Lin S. Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes. BMC Psychiatry. 2012; 12: 47.
Rybakowski JK. Genetic Influences on Response to Mood Stabilizers in Bipolar Disorder. CNS Drugs. 2013; 27: 165–173.
Prabhavalkar KS, Poovanpallil NB, Bhatt LK. Management of bipolar depression with lamotrigine: an antiepileptic mood stabilizer. Front Pharmacol. 2015; 6: 242.
Freeman MP, Stoll AL. Mood Stabilizer Combinations: A Review of Safety and Efficacy. Am J Psychiatry. 1998; 155:12–21.
Core Psychiatry. 3^rd edition.
Pharmacology and Pharmacotherapeutics. 24^th edition.