Mood stabilizers are a group of quite different medicines that share one job: keeping bipolar disorder from swinging into mania or depression. They work by different routes in the brain, so their side effects differ from drug to drug too. Scientists still can’t say exactly how even the oldest one, lithium, works, though it has been used for mania since 1949.1PubMed Central. The history of lithium therapy
Which Drugs Count as Mood Stabilizers
Lithium, valproate and olanzapine clearly calm an acute manic episode.2PubMed. What is a “mood stabilizer”? An evidence-based response Lithium goes further: it also treats acute depression and prevents both mania and depression from returning.3PubMed. What is a “mood stabilizer”? An evidence-based response Lamotrigine’s clear strength is different. It prevents relapses rather than treating an episode already under way.4PubMed. What is a “mood stabilizer”? An evidence-based response In long-term use, lamotrigine prevents relapse about as well as lithium, except that manic symptoms return more often.5Cochrane Database of Systematic Reviews. Lamotrigine for maintenance treatment of bipolar disorder By a strict definition, treating and preventing both poles, only lithium qualifies as a true mood stabilizer.6PubMed. What is a “mood stabilizer”? An evidence-based response
Most of these drugs began as epilepsy medicines and were later found to help mood. Atypical antipsychotics such as olanzapine or quetiapine are used the same way, even though the name sounds unrelated, and being prescribed one for bipolar disorder doesn’t mean your doctor thinks you have psychosis. Many people take two of these together, because one drug rarely covers both poles.
Doctors weigh a few things when choosing. Lithium tends to fit people with a family history of bipolar disorder or a past good response to it, and it is also favoured when suicidal thoughts are present. Valproate fits acute mania, and people with many past episodes or other psychiatric conditions. In long-term use, lithium leads to fewer hospital readmissions than valproate.
How These Drugs Calm the Brain
Valproate raises GABA, the brain’s main “calm down” chemical messenger.7Synapse. What is the mechanism of Sodium Valproate? It also blocks sodium channels, the tiny gates nerve cells use to fire signals.8Synapse. What is the mechanism of Sodium Valproate? And it changes which genes nerve cells switch on, a slower effect that may build over weeks.9PubMed. Valproic acid: Mechanistic insights into neuronal actions, epigenetic modulation, and clinical risk Lamotrigine blocks sodium and calcium gates and reduces glutamate, the brain’s main “excite” messenger.10PubMed Central. Clinical Insights Into the Mechanistic Crossroads of Lamotrigine and Therapeutic Ketosis in Bipolar Depression
Lithium’s route is less certain. It seems to lower inositol, a signalling building block inside cells, and to block an enzyme linked to mood regulation.11PubMed Central. Inositol depletion, GSK3 inhibition and bipolar disorder Valproate shares these two effects, which may explain why both help.12PubMed Central. Inositol depletion, GSK3 inhibition and bipolar disorder Long-term lithium also increases gray matter in some brain regions in people, so it may partly reverse brain shrinkage linked to the illness.13Journal of Clinical Psychiatry. The Use of Mood Stabilizers as Plasticity Enhancers in the Treatment of Neuropsychiatric Disorders
Atypical antipsychotics act on serotonin receptors as strongly as or more than on dopamine receptors.14PubMed Central. Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders That shifts the balance between the two systems, which may underlie their mood effect.15PubMed. Atypical antipsychotics in bipolar depression: neurobiological basis and clinical implications
Benefit takes weeks because calming excitability starts fast, while gene and brain-structure changes build slowly. Feeling better at week one doesn’t mean the full preventive effect is there yet.
Lithium Side Effects and Why Blood Tests Matter
The gap between an effective and a toxic lithium dose is small.16PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring So doses are set by your blood lithium level, measured in mmol/L on your report.17PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring The test is drawn about 12 hours after your last dose.18PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring If you take lithium once a day, the 24-hour level is used instead.19PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring Most doctors aim for 0.6 to 0.8 mmol/L, though some aim for 0.8 to 1.2.20PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring Slow-release tablets are usually kept a bit higher, 0.8 to 1.0.21PubMed. Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring Levels above 1.2 mmol/L can be toxic and can be fatal.22PubMed Central. Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder
Note the time of your last dose for the lab. A test drawn too soon after a dose reads falsely high.
Over years, lithium roughly doubles the risk of moderate chronic kidney disease.23PubMed. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data It more than doubles the risk of an underactive thyroid, and it can raise blood calcium, a sign of overactive parathyroid glands.24PubMed. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data Still, in a group of 1,646 users, only 0.6% developed chronic kidney disease.25PubMed. Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder
On the lab report, eGFR estimates how well your kidneys filter, and it may drift down slowly over years. TSH is the thyroid test; a rising TSH means an underactive thyroid, usually treated with a thyroid pill. Calcium is often checked alongside. Bring past results so trends, not single numbers, are judged.
Worsening shakiness, diarrhea or vomiting, unsteadiness, or confusion warrant same-day medical contact, because they can mean your level is climbing. Dehydration from heat or a stomach bug can push levels up. Some common painkillers and blood pressure drugs can raise them too, so tell every prescriber you take lithium. And don’t take an extra dose to catch up on a missed one.
Valproate Side Effects, From Weight Gain to Pregnancy Risk
At least 1 in 100 people get increased appetite, tremor, drowsiness or hair loss.26Australian Prescriber. Sodium valproate: balancing benefits and risks especially in people of childbearing potential Valproate is the anticonvulsant most linked to weight gain; in one year 71% of users gained weight.27Journal of Clinical Psychiatry. Major System Toxicities and Side Effects of Anticonvulsants The gain may come partly from how the body burns fat, not just eating more.28Journal of Clinical Psychiatry. Major System Toxicities and Side Effects of Anticonvulsants People starting at a normal or low weight gain most often.29Journal of Clinical Psychiatry. Major System Toxicities and Side Effects of Anticonvulsants
Weigh yourself at the start and monthly so gain is caught early. Tell your doctor rather than blaming yourself. Switching or adjusting the dose is a legitimate option to discuss.
Liver damage occurs in about 1 in 20,000 users but can be fatal.30Australian Prescriber. Sodium valproate: balancing benefits and risks especially in people of childbearing potential Yellow skin or eyes, dark urine, severe tiredness or vomiting need urgent care. Liver blood tests are often done in the early months. Risk is higher when several such drugs are combined, and most reported deaths weren’t on valproate alone.31Journal of Clinical Psychiatry. Major System Toxicities and Side Effects of Anticonvulsants
In pregnancy, about 11% of exposed babies had a malformation.32Journal of Clinical Psychiatry. Major System Toxicities and Side Effects of Anticonvulsants These include spina bifida and heart, face and limb defects.33Australian Prescriber. Sodium valproate: balancing benefits and risks especially in people of childbearing potential Anyone who could become pregnant needs reliable contraception and a plan discussed before starting.
Lamotrigine and the Rash to Take Seriously
Lamotrigine can trigger Stevens-Johnson syndrome, a severe skin and mucous membrane reaction.34PubMed Central. Lamotrigine and Stevens-Johnson Syndrome Prevention Serious reactions fell after 1994 once starting doses were lowered.35PubMed Central. Lamotrigine Therapy: Relation Between Treatment of Bipolar Affective Disorder and Incidence of Stevens–Johnson Syndrome—A Narrative Review of the Existing Literature So following the slow dose-increase schedule exactly is the main safety step. People of Chinese, Southeast Asian, Japanese or Korean origin with certain gene variants have higher risk, and the FDA recommends gene testing for these variants before starting.36PubMed Central. Lamotrigine and Stevens-Johnson Syndrome Prevention
Any new rash in the first two months should be reported the same day. Fever, blisters, or mouth or eye sores mean emergency care. Don’t restart old pills after a break of several days without asking; you may need to begin the schedule again. Apart from the rash, lamotrigine lacks the weight gain seen with valproate and antipsychotics. No routine blood level monitoring is needed, unlike lithium.
Carbamazepine, Low Sodium and Drug Interactions
Carbamazepine raises a water-retaining hormone, so the body holds water and dilutes its sodium.37PubMed Central. Carbamazepine-induced hyponatremia – A wakeup call Low sodium affects 1.8% to 40% of users depending on the group, though severe cases on carbamazepine alone are uncommon.38PubMed. Carbamazepine-induced hyponatremia: assessment of risk factors Risk is higher over age 40, in women, and with other sodium-lowering drugs.39PubMed. Carbamazepine-induced hyponatremia: assessment of risk factors
Headache, nausea, confusion or unusual tiredness may signal it, and drinking large amounts of water raises the risk. A simple blood test checks sodium.
Carbamazepine switches on liver enzymes that break it down.40PubMed Central. PharmGKB summary: carbamazepine pathway Blood levels can therefore fall in the early weeks, and doses often need adjusting. Those same enzymes clear many other drugs,41PubMed Central. Pharmacokinetics of the CYP3A4 and CYP2B6 Inducer Carbamazepine and Its Drug–Drug Interaction Potential: A Physiologically Based Pharmacokinetic Modeling Approach so other medicines, including hormonal birth control, may work less well. Carriers of HLA-B*15:02 have about 10 times the risk of Stevens-Johnson syndrome, the severe skin reaction described under lamotrigine, and the FDA recommends testing.42PubMed Central. Pharmacogenomic Characterization in Bipolar Spectrum Disorders
Pharmacists can check interactions each time a new drug is added. Ask specifically about contraception effectiveness. Stopping carbamazepine can make other drugs’ levels rise again.
Antipsychotics Used as Mood Stabilizers
Atypical antipsychotics can cause weight gain, high cholesterol, type 2 diabetes and high blood pressure.43PubMed Central. Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences These can shorten life and make people stop treatment.44PubMed Central. Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences
Weight, waist, blood sugar, cholesterol and blood pressure should be checked at the start and regularly. Early changes in the first months predict later gain. Exercise and diet help, but a different drug may be needed. Report extreme hunger early.
Pregnancy and Breastfeeding
Lithium’s specific birth-defect risk is small, 0.05% to 0.1%, so it is considered the safest mood stabilizer in pregnancy.45PubMed Central. Mood stabilizers in pregnancy and lactation Limited data on lamotrigine don’t show a clear rise in birth defects.46PubMed. Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers Olanzapine, though, raises metabolic complications in pregnant women.47PubMed. Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers Most breastfed infants of mothers on mood stabilizers have no problems.48PubMed. Mood stabilizers during breastfeeding: a systematic review of the recent literature
Discuss plans before trying to conceive, not after a positive test. Stopping suddenly in pregnancy raises relapse risk, which also harms mother and baby. Lithium doses usually need closer monitoring during pregnancy and after birth.
Stopping a Mood Stabilizer Safely
Reducing gradually over at least 4 weeks lowers the chance of severe manic relapse.49PubMed Central. Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder For lithium, tapering over up to 3 months is preferred.50PubMed Central. Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder Mood should be watched for 2 years after stopping.51PubMed Central. Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder
Side effects are the commonest reason people stop, and most have alternatives or fixes. Agree with a doctor on early warning signs like less sleep or racing thoughts, and have a plan for restarting if they appear.