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Information about Medication

TYPES OF MEDICATION
What are mood stabilizers?
Other anticonvulsants used as mood stabilizers
What are antidepressants?
What are antipsychotic medications?
ACUTE PHASE OF TREATMENT
Selecting a mood stabilizer for an acute manic episode
How quickly do mood stabilizers work?
Selecting an antidepressant for an acute depression
Strategies to limit side effects
Electroconvulsive therapy(ECT)
About hospitalization
PREVENTIVE TREATMENT

TYPES OF MEDICATION

Almost all people with bipolar disorder, even those with the most severe forms, can obtain substantial stabilization of their mood swings. The 3 most important types of medication used to control the symptoms of bipolar disorder are mood stabilizers, antidepressants, and antipsychotics. Your doctor may also prescribe other medications to help with insomnia, anxiety, or restlessness. While it is unsure how some of the these medications work, it is known that all of them affect chemicals in the brain called neurotransmitters, which are involved in the functioning of nerve cells.

What are mood stabilizers?

Medications are considered mood stabilizers if they have 2 properties: 1) they provide relief from acute episodes of mania and depression, or prevent them from occurring; and 2) they do not worsen depression or mania or lead to increased cycling.
Lithium, divalproex and carbamazepine meet this definition. The first 2 are the most widely used. Divalproex and carbamazepine were originally developed as anticonvulsants for the control of epilepsy, another brain disorder. Electroconvulsive therapy(ECT), is also considered a mood stabilizing treatment.

Lithium (brand names Eskalith, Lithobid, Lithonate)

The first known mood stabilizer, lithium, is actually an element rather than a compound(a substance synthesized by a laboratory). Lithium was first found to have behavioural effects in the 1950s. Lithium appears to be most effective for individuals with more "pure" or euphoric mania(where there is little depression mixed in with the elevated mood). It is also helpful for depression, especially when added to other medications. Lithium appears to be less effective in mixed manic episodes and in rapid-cycling bipolar disorder. Monitoring blood levels of lithium can reduce side-effects and ensure that the patient is receiving an adequate dose to help produce the best response. Common side-effects of lithium include weight gain, tremor, nausea and increased urination. Lithium may affect the thyroid gland and the kidneys, so periodic tests are needed to be sure they are functioning properly. Lithium users have been known to get "Hypothyroidism" which is the decrease of Thyroid levels. This is why Bipolar Disorder has sometimes been linked to Thyroid Disease.

Divalproex (brand name Depakote)
Divalproex has been used as an anticonvulsant(to treat seizures) for several decades. It has also been extensively researched as a mood stabilizer in bipolar illness. Divalproex is equally effective in both euphoric and mixed manic episodes. It is also effective in rapid-cycling bipolar disorder and for those individuals whose illness is complicated by substance abuse or anxiety disorders. Unlike other mood stabilizers, divalproex can be given in relatively large doses for acute mania, which may produce a more rapid response. Common side effects of divalproex include sedation, weight gain, tremor, and gastrointestinal problems. Blood level monitoring and dose adjustments may help minimize side effects. Divalproex may cause a mild liver inflammation and may affect the production of a type of blood called platelets. Although it is quite rare for there to be any serious complications from these potential effects, it is important to monitor liver function tests and platelet counts periodically.


Other anticonvulsants used as mood stabilizers

  • Carbamazepine (Tegretol, Carbatrol). Although fewer clinical studies support the use of carbamazepine, it appears to have a profile similar to divalproex. It, too, has been available for many years, and is effective in a broad range of subtypes of bipolar illness and in both euphoric and mixed manic episodes. Carbamazepine commonly causes sedation and gastrointestinal side effects. Because of a rare risk of bone marrow suppression and liver inflammation, periodic blood testing is also needed during carbamazepine treatment, just as during treatment with divalproex. Because carbamazepine has complicated interactions with many other medications, careful monitoring is needed when it is combined with other medications.

  • Lamotrigine (Lamictal). Lamotrigine is a relatively new medication. Recent research suggests that it can act as a mood stabilizer, and may be especially useful for the depressed phase of bipolar disorder. One serious risk of lamotrigine use is that 3 out of every 1000 individuals(0.3%) taking the medication develop a serious rash. The risk of rash can be lowered by increasing the dosage very slowly. Aside from the risk of rash, lamotrigine tends to have fewer troublesome side effects overall, but can cause dizziness, headaches, and difficulties with vision.

  • Gabapentin (Neurotonin). Gabapentin has become popular as a mood stabilizer, although there has been relatively little research on its use in bipolar disorder. It appears especially helpful in reducing anxiety. One strength of gabapentin is that it is unlikely to interact with other medications, so that it can be easily added to other mood stabilizers to augment their effect. Side effects of gabapentin can include fatigue, sedation, and dizziness.

  • Topiramate (Topomax). Preliminary research suggests that this new anticonvulsant may be helpful in mania. One side effect of topiramate may actually be an advantage. Unlike many of the other mood stabilizers, topiramate does not appear to cause weight gain and may actually help people lose weight. Other side effects may include sedation, dizziness, and cognitive slowing or memory difficulties. It should be avoided by people who have had kidney stones.

What are antidepressants?

Antidepressants treat the symptoms of depression. In bipolar disorder, antidepressants must be used together with a mood stabilizing medication. If used without a mood stabilizer, an antidepressant can push a person with bipolar disorder into a manic state. Many types of antidepressants are available with different chemical mechanisms of action and side effect profiles. Most research with antidepressants has been done in people with unipolar depression(people who have never had a manic episode). In unipolar depression, the available medications are about equally effective. There has been little research on the use of antidepressants in bipolar disorder, but most experts consider the following 3 types to be first choices:

  • Bupropin (Wellbutrin)
  • Selective serotonin reuptake inhibitors: fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft)
  • Venlafaxine (Effexor)

If these do not work, or they cause unpleasant side effects, the other choices are:

  • Mirtazapine (Remeron)
  • Nefazodone (Serzone)
  • Monoamine oxidase inhibitors: phenelzine (Nardil), tranylcypromine (Parnate). These are very effective but also require you to stay on a special diet to avoid dangerous side effects.
  • Tricyclic antidepressants: amitriptyline (Elavil), desipramine (Norpramin, Pertofrane), imipramine (Tofanil), nortriptyline (Pamelor). Tricyclics may be more likely to cause side effects or to set off manic episodes or rapid cycling.

What are antipsychotic medications?

Antipsychotic medications are used to control psychotic symptoms, such as hallucinations or delusions, that sometimes occur in very severe depressive or manic episodes.
Antipsychotics can be used in 2 additional ways in bipolar disorder, even if no psychotic symptoms are present. They may be used as sedatives, especially during early stages of treatment, for insomnia, anxiety, and agitation. Researchers also believe that the newer antipsychotic medications have mood stabilizing properties, and may help control depression and mania. Antipsychotic medications are therefore often added to mood stabilizers to improve the response in patients who have never had psychotic symptoms. Antipsychotics may also be used alone as mood stabilizers when patients cannot tolerate or do not respond to any of the mood stabilizers.
There are 2 kinds of antipsychotics: older antipsychotics(often called "typical" or conventional antipsychotics) and newer antipsychotics(often called atypical antipsychotics). One serious problem with the older antipsychotics is the risk of a permanent movement disorder called tardive dyskinesia(TD). Older antipsychotic medicines may also cause stiffness, restlessness, and tremors. The newer "atypical" antipsychotics have a much lower risk of causing TD(roughly 1% per year) and movement and muscle side effects. Because of this, the newer atypical antipsychotics are usually the first choice in any of the situations when an antipsychotic is needed.
Four atypical antipsychotics, are currently available:

  • olanzapine (Zyprexa)
  • quetiapine (Seroqeul/Seroquel)
  • risperidone (Risperdal)
  • clozapine (Clozaril)

As mentioned earlier, research is beginning to show that these atypical antipsychotics have mood stabilizing properties. Common side effects of the atypical antipsychotics include drowsiness and weight gain. Although it is very effective, clozapine is not a first choice medication because it can cause a rare and serious blood side effect, requiring weekly or biweekly blood tests.
Examples of conventional antipsychotics include older medications such as:

  • haloperidol (Haldol)
  • perphenazine (Trilafon)
  • chlorpromazine (Thorazine)

Although they are not usually a first choice, the older medications can be helpful for patients who do not respond to or have troublesome side effects with the newer atypical antipsychotics.

ACUTE PHASE OF TREATMENT

Selecting a mood stabilizer for an acute manic episode

The first-line drugs for treating a manic episode during the acute phase are lithium and valproate. In choosing between these 2 medications, your doctor will consider your treatment history(whether either of these medicines has worked well for you in the past), the subtype of bipolar disorder you have(e.g., whether you have rapid cycling bipolar disorder), your current mood state(euphoric or mixed mania), and the particular side effects that you are most concerned about.
Lithium and divalproex are each good choices for "pure" mania(euphoric mood without symptoms of depression), while divalproex is preferred for mixed episodes or for patients who have rapid cycling bipolar disorder. It is not unusual to combine lithium with divalproex to obtain the best possible response. If this combination is still not fully effective, a third mood stabilizer is sometimes added.
Carbamazepine is a good alternative medication after lithium and divalproex. Like divalproex, carbamazepine may be particularly effective in mixed episodes and in the rapid cycling subtype. It can be easily combined with lithium, although it is more complicated to combine it with divalproex.
The newer anticonvulsants(lamotrigine, gabapentin, and topiramate) are often best reserved as back-up medications to add to first-line medications for mania, or to use instead of the first-line group if there have been difficult side effects.

How quickly do mood stabilizers work?

It can take a few weeks for a good response to occur with mood stabilizers. However, it is often helpful to combine mood stabilizers with other medications that provide immediate, short-term relief from the insomnia, anxiety, and the agitation that often occur during a manic episode. The choices for so-called "adjunctive" medication include:

  • antipsychotic medicines, especially if the person is also having psychotic symptoms(see above)
  • a sedative called a benzodiazepine. Benzodiazepines include lorazepam (Activan), clonazepam (Klonopin), and others. They should be carefully supervised, or avoided, in patients who have a history of drug addiction or alcoholism.

Although both benzodiazepine sedatives and antipsychotic medicines can cause drowsiness, the dosages of these medications can generally be lowered as the person recovers from the acute episode. However, some individuals need to continue taking a sedative for a longer period to control certain symptoms such as insomnia or anxiety. Longer-term treatment with an antipsychotic is sometimes needed to prevent relapse.

Selecting an antidepressant for an acute depression

Although a mood stabilizer may treat milder depression, an antidepressant is usually needed for more severe depression. It is dangerous to give antidepressants alone in bipolar disorder, because they can trigger an increase in cycling or cause the person's mood to "overshoot" and switch from depression to hypomania. For this reason, antidepressants are always given in combination with a mood stabilizer in bipolar disorder.
Antidepressants usually take several weeks to show effects. Although the first antidepressant tried will work for the majority of patients, it is common for the patients to go through 2 or 3 trials of antidepressants before finding one that is fully effective and doesn't cause troublesome side effects. While waiting for the antidepressant to work, it may may be helpful to take a sedating medication to help relieve insomnia, anxiety, or agitation.
If depression persists despite use of an antidepressant with a mood stabilizer, adding lithium(if not already in use) or changing the mood stabilizer might help. Lamotrigine, in particular, may be helpful in depression.

Strategies to limit side effects

All of the medications that are used to treat bipolar disorder can produce bothersome side effects; there are also some serious but rare medical reactions. Just as different people have varying responses to different medications, the type of side effects different people develop can vary widely, and some people may not have any side effects at all. Also, if someone has problems with side effects on 1 medication, this does not mean that the person will develop troublesome side effects on another medication,
Certain strategies can help prevent or minimize side effects. For example, the doctor may want to start at a low dose and adjust the medication to higher doses very slowly. Although this may mean that you need to wait longer to see if the medication will help the symptoms, it does reduce the chances of side effects developing. In the case of lithium or divalproex, blood level monitoring is very important to insure that a patient is receiving enough medication to help, but not more than is necessary. If side effects do occur, the dosage can frequently be adjusted to eliminate the side effects or another medication can be added to help. It is important to discuss your concerns about side effects and any problems you may be experiencing with your doctor, so that he or she can take it into account when planning your treatment.

Electroconvulsive therapy (ECT)

Electroconvulsive therapy is often life-saving in severe depression and mania, but has received a lot of undeserved negative publicity. ECT is a critically important option if someone is very suicidal, if the person is severely ill and cannot wait for medications to work(e.g., the person is not eating or drinking), if there is a history of many unsuccessful medication trials, if medical conditions or pregnancy make medications unsafe, or if psychosis(delusions or hallucinations) is present. ECT is administered under anesthesia in a carefully monitored medical setting. Patients typically receive 6 to 10 treatments over a few weeks. The most common side effect of ECT is temporary memory problems, but memory returns quickly after a course of treatment.

About hospitalization

Many patients with bipolar I disorder(i.e., patients who have had at least 1 full manic episode) are hospitalized at some point in the course of the illness. Because acute mania affects insight and judgment, individuals with mania are often hospitalized over their objections, which can be upsetting for both patients and their loved ones. However, most individuals with mania are grateful for the help they received during the acute episode, even if it was given against their will at the time. Hospitalization should be considered under the following circumstances:

  • When safety is a question due to suicidal, homicidal, or aggressive impulses or actions
  • When severe distress or dysfunction requires round-the-clock care and support(which is difficult, if not impossible, for any family to sustain for a long period of time)
  • Where there is ongoing substance abuse, to prevent access to drugs
  • When the patient has an unstable medical condition
  • When close observation of the patient's reaction to medications is required

PREVENTIVE TREATMENT

Mood stabilizers, especially lithium and divalproex, are the cornerstones of prevention for long term maintenance treatment. About 1 in 3 people with bipolar disorder will remain completely free of symptoms just by taking mood stabilizing medication for life. Most other people experience a great reduction in the frequency and severity of episodes during maintenance treatment.
It is important not to become overly discouraged when episodes do occur and to recognize that the success of treatment can only be evaluated over the long term, by looking at the frequency and severity of episodes. Be sure to report changes in mood to your doctor immediately, because adjustments in your medicine at the first warning signs can often restore normal mood and head off a full-blown episode. Medication adjustments should be viewed as a routine part of treatment(just as insulin doses are changed from time to time in diabetes). Most patients with bipolar disorder do best on a combination or "cocktail" of medications. Often the best response is achieved with 1 or more mood stabilizers, supplemented from time to time with an antidepressant or possibly an antipsychotic medication.
Continuing to take medication correctly and as prescribed(which is called adherence) on a long term basis is difficult whether you are being treated for a medical condition(such as high blood pressure or diabetes) or for bipolar disorder. Individuals with bipolar disorder are often tempted to stop taking medication during maintenance treatment for several reasons. They may feel free of symptoms and think they don't need medication any more. They may find the side effects too hard to deal with. Or they may miss the mild euphoria they experience during hypomanic episodes. However, research clearly indicates that stopping maintenance medication almost always results in relapse, usually in weeks to months after stopping. In the case of lithium discontinuation, the rate of suicide rises precipitously. There is some evidence that stopping lithium in an abrupt fashion(rather than slowly tapering off) carries a much greater risk of relapse. Therefore, if you must discontinue medication, it should be done gradually under the close medical supervision of your doctor.
If someone has had only a single episode of mania, consideration may be given to tapering the medication after about a year. However, if the single episode occurs in someone with a strong family history of bipolar disorder or is particularly severe, longer term treatment should be considered. If someone has had 2 or more manic or depressed episodes, experts strongly recommend taking preventive medication indefinitely. The only times to consider stopping a preventive medication that is working well is if a medical condition or severe side effects prevent its safe use, or when a women is trying to become pregnant. Even these situations may not be absolute reasons to stop, and substitute medications can often be found. You should discuss each of these situations carefully with your doctor.

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© Mark Hannant
Published 2nd May 2001