Mood stabilising drugs
A variety of chemotypes are grouped together as the mood stabilising drugs, used in the management of bipolar disorder (manic depression), mania and hypomania, and sometimes recurrent severe depression. Naming these drugs as mood stabilisers belies their action of stabilising mood in patients who experience problems with extreme highs, extreme lows, or mood swings between extreme highs and lows.
Mood stabilisers should only be prescribed by mental health professionals, such as psychiatrists.
Lithium (Li+) is a natural inorganic substance, administered as carbonate or citrate salts. In addition to being used to manage bipolar disorder, lithium can also be used to manage recurring depression, schizoaffective disorder, self-harm and some aggressive behaviours. Blood lithium levels must be monitored regularly to maintain safe levels (<1.5mmol/l), and dose must be titrated for individual patients. One advantage that lithium has over other mood stabilising drugs is that it does not cause sleepiness or drowsiness. Patients should ask for advice from their health care professional before taking any non-prescription medicines alongside lithium, as some of these medicines (e.g. ibuprofen) can alter the body's ability to excrete lithium, or alter fluid balance (as can some herbal and other complementary medicines) which indirectly alters blood lithium levels. The most common side-effects are thirst, nausea, dizziness, mild diarrhoea, and a metallic taste in the mouth, and taking lithium may cause weight gain. Signs of lithium overdose include loss of coordination, heavy tremors, muscle stiffness, difficulty speaking, confusion and in severe cases results in stupor, coma and even death.
Carbamazepine, lamotrigine and valproate (valproic acid) were originally used as antiepileptic medications, but are primarily now used as mood stabilisers. The molecular mechanisms of action of these drugs are poorly defined, but are suggested to involve inhibition of sodium and/or calcium channels.
Carbamazepine is used to manage bipolar disorder. It is not suitable for treating recurrent depression or acute mania. As with lithium, regular blood test should be used to monitor for safe and effective therapeutic levels. Taking carbamazepine alongside SSRI (selective serotonin reuptake inhibitor) and tricyclic antidepressants can make the antidepressants less effective. Monoamine oxidase inhibitor (MAOI) antidepressants can increase carbamazepine to dangerous levels, so medical advice is to wait for 2 weeks after coming off MAOIs before beginning carbamazepine therapy. Carbamazepine can make oral contraceptives less effective, so alternative methods of contraception should be considered. Common side-effects include dizziness, tiredness, nausea, vomiting, skin reactions, increased susceptibility to infection (related to reduced white blood cell counts), dry mouth, headaches, blurred/double vision and weight gain.
Lamotrigine is prescribed for managing depression in bipolar disorder. An initial low dose should be trialled and increased if necessary, to reduce the likelihood of developing serious skin reactions, which is the most common lamotrigine side-effect. Other common side-effects include headaches, dry mouth, irritability, sleepiness, dizziness, nausea and vomiting. Carbamazepine can lower blood levels of lamotrigine, so the lamotrigine is likely to be less effective. Oral contraceptive pills can affect lamotrigine metabolism, so dosage modifications or alternative methods of contraception should be considered.
Valproate is prescribed for managing mania in bipolar disorder. Valproate is not usually suitable for recurrent depression. Common side-effects include nausea, vomiting, tremor, unsteadiness, loss of appetite and fluid retention. Valproate interacts with many other mood stabilisers and antidepressants. It increases levels of lamotrigine and carbamazepine, and levels of MAOI and tricyclic antidepressants, increasing the risk of unpleasant side-effects. Taking valproate with the antipsychotic, olanzapine can increase the likelihood of experiencing liver problems, weight gain and low white blood cell counts.
Asenapine is an atypical antipsychotic drug, but its main use is as a mood stabiliser. Its primary molecular action is as a serotonin and dopamine receptor antagonist, in particular antagonism of the dopamine D2 and serotonin 5-HT2A and 5-HT2C receptors. This multireceptor mechanism helps to normalise the activity of the brain, reducing manic symptoms. Asenapine is prescribed for managing mania in bipolar disorder. Common side-effects are extreme sleepiness and anxiety. Asenapine can increase circulating levels of the SSRI antidepressant, paroxetine, which increases the risk of unpleasant side effects.