Carbamazepine is an anticonvulsant drug, chemically related to the tricyclic antidepressants.
Carbamazepine is effective in controlling impulsive and aggressive behavior. As a mood stabilizer, it is generally felt to be inferior to both lithium and valproic acid and it has a much worse side effect profile than valproic acid.
Up to 50% of patients receiving carbamazepine experience side effects, and the drug is associated with potentially serious adverse reactions
- Aplastic anemia
- Hepatic toxicity
- Impaired learning and memory
- Emotional affects such as irritability and agitation
- Changes in vision
- Water retention
- Weight gain
The most commonly seen side effects with this agent in children are drowsiness, loss of coordination, and vertigo. Overdose of Carbamazepine can be fatal.
Oxcarbazepine is a chemical analogue of carbamazepine. The chemical difference translates to a more favorable adverse-effect profile when compared with carbamazepine.
- Upper respiratory tract infection
Each of these side effects occurred in at least 5% of patients. Another significant side effect occurring in 2.5% of patients is low sodium blood levels.
Even though oxcarbazepine seems to be a better alternative to carbamazepine, its usefulness in the treatment of agitation, aggression and impulsivity has not been scientifically verified.
Although the FDA has approved lamotrigine for use in "mood episodes," studies show that it is only effective in preventing depression. In mania, it seems less effective than other drugs.
Serious rash is itâ€™s only major side effect, and it occurs more frequently in children than in adults. There are no data on lamotrigineâ€™s efficacy as mood stabilizers in children or adolescents.
The major advantage of gabapentin is its relative safety and lack of interactions with other drugs. Its major drawback is that it doesnâ€™t work. Parke-Davis sponsored a study in preparation to an FDA application for use as a mood stabilizer and found it was no better than placebo. In combination with other medications, gabapentin seems to be helpful in managing anxiety and aggression.
Topiramate is yet another anticonvulsant with mood stabilizing effects for some patients. It seems to help with anxiety and a number of eating disorders. It is being used clinically to counteract the weight gain caused by valproic acid.
The most common adverse events were sweating, blurred vision, difficulty sleeping, tremors, and paresthesia.
Levetiracetam is an anticonvulsant approved in the US in late 1999. There are now anecdotal reports of its action as a mood stabilizer.
There are seven distinct classes of antidepressants. The tricyclic antidepressants and monoamine oxidase inhibitors have been around the longest. The serotonin selective reuptake inhibitors are the most popular antidepressants used today. Three other classes also affect the serotonin system, but have additional affects on other systems. These are the dual serotonin and norepinephrine reuptake inhibitors, the serotonin-2 antagonism/reuptake inhibitors, and alpha2 antagonism plus serotonin-2 and -3 antagonizers. The final category is the norepinephrine reuptake inhibitors.
Antidepressants tend to work slowly. It usually takes several weeks before they begin to work and it may take as much as three months before their full benefit is realized. Most antidepressants cause a weight gain of about ten pounds within the first six months. Many cause sexual dysfunction. They also tend to interact negatively with many other drugs. These drugs must be used carefully in bipolar depression, because they have a tendency to push the patient into a manic episode.
Monoamine Oxidase (MAO) Inhibiters
The MAO inhibitors were discovered in the 1950â€™s and were the first antidepressant drugs. These drugs cause dangerous hypertension reactions in patients who take these drugs and who ate certain common foods (cheese) or used certain medications.
These drugs are still used in patients who fail on safer drugs. They are helpful in controlling depression and anxiety.
- Phenelzine (Nardil)
- Isocarboxazid (Marplan )
- Tranylcypromine (Parnate )
Tricyclic Antidepressants (TCAs)
As mood stabilizers, the newer antidepressants have eclipsed the tricyclic antidepressants. However, in the treatment of ADHD, these drugs are very effective. They help 70% of children who fail on stimulants.
The most common drugs in this category are imipramine (Tofranil), nortriptyline, and desipramine (Norpramin). In practice, we have more clinical experience with imipramine, but there is mounting evidence that desipramine may be the better choice.
Imipramine and desipramine have played an important role in research. These drugs have been used as the control drugs when testing the newer antidepressants. In general, all the newer drugs have been better mood stabilizers than the tricyclic antidepressants. However, the TCAs are still considered a better choice in ADHD children, and in ADHD children with other psychiatric disorders such as depression or anxiety disorder they may work better than the stimulants.
Serotonin Selective Reuptake Inhibitors (SSRIs)
These are the most popular antidepressants used today. In general, they work better than the older tricyclic antidepressants and have fewer side effects.
Long-term use of these drugs is associated with significant weight gain and sexual dysfunction.
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
- Citalopram (Celexa, Cipramil)
- Sertraline (Zoloft)
Serotonin and Norepinephrine Re-uptake Inhibitors (SNRIs)
Venlafaxine is the paradigm drug in this category. It tends to work better than the SSRIs, but is associated with the increase of aggressive behavior when used together with clonidine.
Other Classes of Serotonin Uptake Inhibiters
Nefazodone inhibits serotonin and norepinephrine reuptake. It has an advantage over the SSRIâ€™s in that it causes fewer gastrointestinal side effects and does not cause weight gain or sexual dysfunction.
Mirtazapine has a weaker antidepressant effect than other drugs, but it seems to be more effective against anxiety disorders. Mirtazapine is associated with significant weight gain early in therapy.
Norepinephrine Reuptake Inhibitors
Bupropion ( Amfebutamone, Wellbutrin, Zyban )
Bupropion is a selective norepinephrine and dopamine reuptake inhibitor. It is as effective an antidepressant as the SSRIâ€™s and has fewer side effects. Bupropion does not cause sexual dysfunction and is less likely than other antidepressants to induce mania in bipolar patients.
Reboxetine is a selective norepinephrine reuptake inhibitor similar to Strattera. Reboxetine itself typically doesn't have the disruptive effects on cognitive function or psychomotor performance common to older antidepressants. I have seen this drug used successfully in the management of ADHD patients who did not do well with stimulants or other antidepressants. I have also seen this drug induce Raynaudâ€™s syndrome in one child, which is not a reported side effect of the drug.
This drug is licensed in over 50 countries. However, the FDA declined Pharmacia's license application for the North American market. This was a surprising event, considering the FDA approved a similar drug, Strattera, a short time later. The FDA has not revealed the grounds for the decision, but I have my suspicions.
Anti-Psychotic Drugs (Neuroleptics)
These are not really mood stabilizers, but in practice they are used short term and in low doses to control some of the symptoms that accompany mood disorders. These drugs have significant long-term side effects and risks so they are not commonly used as a maintenance drug in mood disorders.
There are a lot of ADHD children with bipolar disorder on this drug. It has received FDA approval for the short-term treatment of manic episodes.
The most common side effects are restlessness, tremors, muscle stiffness, sleepiness, nausea, abnormal vision, increased saliva, abdominal pain, and urinary incontinence.
Olanzapine is an anti-psychotic drug that has received FDA approval for the treatment of acute mania, although it has on occasion induced mania. On the whole olanzapine is a very effect mood stabilizer and it appears that it might be a good maintenance drug.
Olanzapine has side effects similar to other anti-psychotic drugs, though like other newer anti-psychotics, these side effects are less severe than with older drugs.
Clozapine is effective both in unresponsive mood disorders.
There are numerous drugs being used as mood stabilizers and there are going to be a lot more. The current trend is toward using these drugs more often to manage short-term and long-term behavior and mood disorders.
Although these drugs all have serious long-term side effects, they are usually fairly safe short-term if the patient is managed closely.
Anthony Kane, MD
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