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Does lamotrigine cause weight loss: Effectiveness and Weight Effects of Open-Label Lamotrigine With and Without Concomitant Psychotropic Medications in Patients With Bipolar I Disorder

Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder

Randomized Controlled Trial

. 2006 Apr;8(2):175-81.

doi: 10.1111/j.1399-5618.2006.00308.x.

Gary Sachs 
1
, Charles Bowden, Joseph R Calabrese, Terence Ketter, Thomas Thompson, Robin White, Beth Bentley

Affiliations

Affiliation

  • 1 Department of Psychiatry, Harvard University, Harvard Bipolar Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. [email protected]
  • PMID:

    16542188

  • DOI:

    10.1111/j.1399-5618.2006.00308.x

Randomized Controlled Trial

Gary Sachs et al.

Bipolar Disord.

2006 Apr.

. 2006 Apr;8(2):175-81.

doi: 10.1111/j.1399-5618.2006.00308.x.

Authors

Gary Sachs 
1
, Charles Bowden, Joseph R Calabrese, Terence Ketter, Thomas Thompson, Robin White, Beth Bentley

Affiliation

  • 1 Department of Psychiatry, Harvard University, Harvard Bipolar Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. [email protected]
  • PMID:

    16542188

  • DOI:

    10.1111/j.1399-5618.2006.00308.x

Abstract


Objective:

The effect of lamotrigine maintenance therapy on body weight was assessed retrospectively in analyses of data from two double-blind, placebo- and lithium-controlled, 18-month studies in patients with bipolar I disorder (n = 227 for lamotrigine, 190 for placebo, 166 for lithium).


Methods:

Endpoints included mean change in weight, the percentage of patients with > or = 7% change (increase, decrease, fluctuation) in weight, and the percentage of patients with weight-related adverse events during double-blind treatment.


Results:

Mean weight remained stable during maintenance therapy with lamotrigine. In a mixed-model repeated-measures analysis, mean changes in weight (kg) at week 52 were -1.2 with lamotrigine, +0.2 with placebo, and +2.2 with lithium [estimated difference (95% CI) lamotrigine minus placebo = -1.3 (-3.6, 0.9), p = 0.237; lithium minus placebo = +2.0 (-0.3, 4.4), p = 0.094; lithium minus lamotrigine = +3.4 (1.4, 5.4), p < 0.001]. Analyses were truncated at week 52 because of the high incidence of missing data at later time points. The percentages of patients with a >/=7% weight gain, during randomized treatment, were 10. 9%, 7.6% and 11.8% for the lamotrigine, placebo, and lithium groups, respectively. The percentages of patients with a > or = 7% weight loss, during randomized treatment, were 12.1%, 11.5%, and 5.1% for the lamotrigine, placebo, and lithium groups, respectively. The percentage of patients with a > or = 7% weight loss did not significantly differ between lamotrigine and placebo but was significantly higher with lamotrigine than lithium. The incidences of > or = 7% weight changes and of weight changes reported as adverse events were comparable between active treatments and placebo.


Conclusion:

Lamotrigine was associated with stable body weight during 1 year of treatment and was comparable to placebo in mean weight change, incidence of clinically significant weight change, and incidence of weight changes reported as adverse events in patients with bipolar disorder. Lithium was associated with weight gain, but the magnitude of lithium-associated weight gain was lower in the current analysis than in previous studies.

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Publication types

MeSH terms

Substances

Bipolar Medications and Weight Loss

Introduction

Bipolar disorder can be treated with medications from different drug groups. These groups include mood stabilizers, antipsychotics, and antidepressants. The drugs in each of these groups affect your body differently, including how they affect your weight. Here’s a look at how some of the more common drugs for bipolar disorder affect your weight, plus their other side effects.

Most bipolar drugs cause weight gain rather than weight loss. For example, several of them increase your blood sugar level, which can lead to weight gain. Others affect your energy level. During manic episodes, you typically may not sleep much and may burn off lots of energy. Taking a bipolar drug can calm your mood and help you sleep. In turn, these effects could decrease the amount of energy your body burns. This can lead to an increase in weight, especially if you don’t adjust your diet. However, the way that these drugs can affect your weight varies.

Mood stabilizers

Low risk of weight gain: Lamotrigine (Lamictal) is most likely to cause weight loss. However, it can also cause weight gain. Other common side effects of this drug include:

  • headache
  • trouble sleeping
  • drowsiness
  • upset stomach
  • aches and pains throughout your body

Risk of weight gain: Valproate is likely to cause weight gain. It may also cause tremors, headaches, dizziness, and nausea.

High risk of weight gain: Lithium is known for causing weight gain. Common side effects of this drug also include:

  • sleepiness
  • fatigue
  • low blood pressure
  • slowed thyroid function
  • mild nausea

Antipsychotics

Low risk of weight gain: Lurasidone has a low risk of weight gain. Other side effects of this drug may include the development of breasts in men, low blood pressure, and fainting.

Risk of weight gain: Quetiapine can cause weight gain. Common side effects may also include:

  • changes in blood pressure
  • nausea
  • cataracts
  • development of breasts in men
  • reduced thyroid function

High risk of weight gain: Olanzapine is very likely to causeweight gain because it increases your appetite. Other common side effects can include:

  • dry mouth
  • thirst
  • frequent urination
  • constipation
  • dizziness
  • sleepiness
  • weakness
  • movement disorders and tremor

There are several different drugs available to treat bipolar disorder. Most of them affect your weight, but many increase your risk of weight gain rather than weight loss. By making healthy choices in your diet and adding routine exercise, you may be able to minimize these effects.

Many people with bipolar disorder often have to try several different drugs before finding one that works. Talk to your doctor and balance your concerns about weight gain with the likelihood of a certain drug working well for you. Tell your doctor about your health history, your family’s health history, and your concerns about how treatment will affect your weight. This information will help your doctor understand which drugs are more likely to work well for you.

Lamotrigine

Lamotrigine is an anticonvulsant drug used to treat various forms of epilepsy and mood disorders in bipolar disorder.

Synonyms Russian

Lamictal, lameptil, convulsan, lamitor, lamolep, lamotriks, seizar, triginet.

English synonyms

Lamotrigin, Lamictal.

Test Method

Gas Chromatography-Mass Spectrometry (GC-MS).

Units

μg/mL (micrograms per milliliter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for an examination?

  • Do not eat for 2-3 hours before the examination, you can drink pure non-carbonated water.
  • Children under 1 year of age should not eat for 30-40 minutes prior to testing.
  • Do not smoke for 30 minutes before the test.

Overview of the study

Lamotrigine is a broad-spectrum antiepileptic drug for various forms of epilepsy that may have beneficial effects on mood in bipolar disorders. The drug is used as mono- or additional therapy for partial and generalized convulsive seizures, seizures with Lennox-Gastaut syndrome, with typical absences, as well as for the prevention of mood disorders (depression, mania, hypomania) in patients with bipolar disorder. In addition, lamotrigine is being considered for migraine, trigeminal neuralgia, and treatment-refractory depression.

Its pharmacological action is associated with the blocking of voltage-gated sodium channels, stabilization of the nerve cell membrane and suppression of the release of glutamic acid.

The bioavailability of lamotrigine is very high at 98%. After oral administration, the drug is quickly and fairly completely absorbed from the gastrointestinal tract, food intake slows down the absorption process, but does not reduce its effectiveness. The maximum concentration in the blood is observed 2.5 hours after ingestion. Binding to blood proteins is not more than 55%. Therapeutic concentration in the blood is 2. 5-15 mcg / ml. Lamotrigine is metabolized in the liver by conjugation with glucuronic acid using the enzyme glucuronyl transferase and without the participation of the cytochrome P450 system. The elimination half-life of lamotrigine is 24-35 hours and depends on the co-administered medicinal products. The drug is excreted from the body mainly by the kidneys in the form of glucuronides or unchanged (10%), and about 2% – through the intestines.

While taking lamotrigine, headache, fatigue, drowsiness or insomnia, nausea, vomiting, a decrease in the number of leukocytes and platelets in the blood, skin rashes and allergic reactions may occur, in rare cases, Stevens-Johnson syndrome, Lyell’s syndrome may develop. In some cases, abrupt discontinuation of the drug can provoke epileptic seizures, so when you cancel lamotrigine, the dose should be reduced gradually.

The concentration of the drug in the blood should be monitored and corrected in hepatic and renal failure, while taking with other drugs. It is also important to consider fluctuations in blood levels of lamotrigine during pregnancy and postpartum ( Fetal Category FDA – C). During pregnancy, there is a decrease in the concentration of lamotrigine in the blood due to an increase in body weight and increased excretion under the influence of estrogens. This circumstance can lead to a worsening of the course of the disease. On the other hand, after childbirth, due to the reverse development of the above processes, physiological conditions are created for the appearance of signs of intoxication. Therefore, when planning pregnancy in women taking lamotrigine, it is advisable to determine the level of the drug in the blood and monitor it during pregnancy and after childbirth.

What is research used for?

  • Blood drug concentration monitoring;
  • drug interaction assessment;
  • diagnosis of overdose;
  • detection of violations of the drug regimen.

When is the examination scheduled?

  • If symptoms persist or worsen while taking lamotrigine;
  • while prescribing other anticonvulsants that affect the concentration of lamotrigine in the blood;
  • if the patient has impaired liver and kidney function;
  • before and during pregnancy and after childbirth;
  • for adverse events likely to be related to lamotrigine and suspected drug overdose.

What do the results mean?

Reference values: 4 – 10 µg/ml.

What can influence the result?

  • The concentration of lamotrigine in the blood increases:
    • when taking valproic acid;
    • for violations of the liver and kidneys.
  • Medicines that can reduce the concentration of lamotrigine in the blood: phenytoin, carbamazepine, phenobarbital, primidone, oral contraceptives, estrogens.

Important Notes

  • It is recommended to take blood for research 30-60 minutes before the scheduled intake of the drug.
  • Treatment, dose adjustment of this drug and concentration monitoring is carried out strictly under the supervision of a physician. It is unacceptable to independently change the mode of administration and dose of the drug.

Also recommended

[02-014] CBC

[06-003] Alanine aminotransferase (ALT)

[06-010] Aspartate aminotransferase (AST)

[06-036] Bilirubin total

[ 06-021] Serum creatinine

[15-001] Valproic acid

[15-006] Topiramate

Who orders the test?

Psychiatrist, psychotherapist, neurologist, clinical pharmacologist.

Literature

  • Adab N. Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful? CNS Drugs. 2006;20(10):791 – 800.
  • Cassels C. Lowering of Lamotrigine blood levels linked to increased seizure risk during pregnancy. Medscape. Nov 28, 2007.