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Treatment of Bipolar Disorder by M. Glaser, MD WHAT ARE THE TREATMENTS FOR BIPOLAR DISORDER? Bipolar disorder requires medication, usually life long. Most patients treated for bipolar disorder require more than one medication to control the symptoms. You can compare it to the treatment of high blood pressure. Like in high blood pressure, one can live a lifestyle that is healthy and take medication to have the best outcome possible. Treated and controlled high blood pressure is not problematic. Untreated high blood pressure is severely problematic. Well, bipolar disorder is the same. If a person with bipolar disorder lives a healthy lifestyle and takes medication, then severe problems are usually prevented. The medications preserve brain functioning and prevent brain damage that bipolar disorder causes. Bipolar disorder has two parts, mania and depression. Some medications treat the mania as well as anger while others treat only depression while others treat both. First I will describe the medications that treat mania and then the medications that treat both mania plus depression. It is important to note, I will succinctly describe each medication with its most serious side effects. For all the medications I list below, their serious side effects are extremely rare and infrequent. However, I will not sugar cote the information. Some side effects are not entirely known, therefore there are times when I give you my editorial opinion based on my experience and knowledge as a physician. New side effects are often discovered years after a medication is introduced. The medications for bipolar disorder fall into three main groups. One is the second generation antipsychotics, second is the antiseizure medications, and third is lithium. Lithium is the oldest treatment for bipolar disorder and has been used in psychiatry for several decades. Some say that Cuban cigars are so well liked because of the high amounts of lithium in Cuban soil. Lithium works best for classic bipolar disorder that includes distinctive episodes of mania (high energy plus euphoria) not mixed with other symptoms like hallucinations or depression. Lithium is very inexpensive to prescribe and since it has been around so long, its side effects are generally understood. Most people who take lithium do not have any serious side effects. The serious ones include hypothyroidism (this means low thyroid hormone which regulates your metabolism so if it is hypo you will feel tired and cold). Other important side effect risks are a hand tremor, acne, weight gain and increased urination do to kidney irritation and possible injury. Hair loss can also happen. In growing bones, lithium does get deposited in the bone structure, with unknown effects. Periodic blood levels must be checked for lithium to make sure the level is not to low or to high. Lithium at too high a blood level in you body can be toxic and cause a heart attack. The window is narrow. The second oldest group of medications with known benefits for bipolar disorder are the antiseizure medications. These are Depakote, Tegretol, Lamictal, and Trileptal. Other antiseizure medications such as Neurontin and Trileptal are also used for bipolar disorder but there are no studies supporting there use for bipolar in children and spars data for treatment in adults. In fact there is evidence that they are not effective. Trileptal's benefit for bipolar, in my opinion, has not been completely settled. First is Depakote (valproic acid). This has FDA approval to treat manic(increased energy plus euphoria) and mixed(increased energy plus depression or rage) episodes. It has no proven benefit for depressed episodes nor have I seen it help depressed episodes in my practice. My experience with Depakote is that most patients gain lots of weight. Depakote also requires monitoring of blood periodically to check for potential liver injury and low blood counts. There is one study of patients in Europe. The patients were all female with seizures who took Depakote prior to puberty. There was an extra ordinary high rate of polycystic ovary disease which causes sterility possibly due to a Depakote side effect. Please note that these are all extremely, extremely, rare side effects. Also, since we know what level Depakote must be at in your system to know if it will work, we also periodically check blood levels of the med. Too high a level can be toxic and too low will not help. Tegretol (carbemazapine) is the second most common antiseizure medication used for bipolar disorder. There is not as much evidence for it as there is for Depakote but a considerable amount of data shows it to be effective for manic phases. Some psychiatrists prefer Depakote and Tegretol for anger problems but I prefer the second generation antipsychotics for anger/rage issues. Tegretol has very very rare but serious side effects. The overwhelming majority of patients do not experience them just like with most of the medications I describe in this section, the side effects generally do not happen. However, Tegretol's risks include low white blood cell count. If this happens, the patient is unable to fight off infections. Thus, blood must be checked periodically. Another rare but serious side effect is Stevens-Johnson syndrome. This is a rash that is so severe it could kill the person. Blood levels must be checked to avoid too low a level or too high a level that could be toxic. While taking this medication, notify your doctor if you experience any rash and stop taking Tegretol until you talk to your doctor. You should also take Benadryl 50 mg every 12 hours and apply hydrocortisone cream to the rash four times a day. Lamictal is the newest antiseizure medication for bipolar disorder. It was the first to be approved by the FDA for the depressed phase of bipolar disorder. It has also shown to help mania as well. Weight gain does not occur as much as with Depakote. Blood draws are not required. It is newer, so side effects are not as well established as with Depakote and Tegretol. The most serious side effect is a rash similar to Tegretol but with greater frequency. The rash is called Stevens-Johnson syndrome and can be deadly. If you get a rash of any size, stop taking Lamictal and call your doctor emergently. Follow the instructions above for Tegretol. In order to minimize the risk of a rash, the dose of lamictal is started very low and takes several weeks or months to get to a therapeutic level. My experience with this medication is more limited than with the others. However, I have yet to be impressed with its efficacy. Topomax, is a great medicaton because it usually causes weight loss and thus is very expensive. However, there are no studies supporting its use in bipolar disorder and it may even worsen a person's mood. Topomax can cause a person to feel mentally slow. On the other hand, Topomax is a fantastic anti-migraine head ache medication. It works great, when taken every day, at preventing migraine head aches. The next group are the second generation antipsychotic medications. These medications were originally invented to treat psychosis (delusions or hallucinations) but were then discovered to help bipolar disorder as well. Most are FDA approved to treat bipolar disorder and are now nearly as often prescribed for bipolar as they are for psychosis. The names of these medications are Zyprexa, Abilify, Risperdal, Seroquel, and Geodon. Geodon has no FDA approval for bipolar disorder so it will not be discussed here. The "grand daddy" of all psych meds is Clozapine, but due to its severe risk of side effects, it also will not be discussed here, other than the fact that it probably works the best. My first choice in this group of medications is Abilify (aripiprazol). I have found that it is the best tolerated by my patients. It has been shown in studies to treat mania, mixed episodes, and adjunctive treatment of another illness called major depression. It has not yet been shown to help bipolar depression. Its main side effect risk is tardive diskenesia. This is a permanent, slow writhing movement of the hands, body, or face. This risk is very rare and I have yet to see it in my practice resulting from Abilify. All medications in this class have a very low risk of diabetis. It is likely, but not proven that Abilify's risk is the lowest within this group at causing diabetis. Again, this risk is very, very low. The benefits if Abilify versus the other medications to chose from are as follows. It generally does NOT cause tiredness or a "zombie" feeling and it usually does not cause weight gain. It also does not raise cholesterol like the other meds in the group can do. Another huge benefit is that Abilify has a unique mechanism of action that allows it to also help with improving attention span and reducing hyperactivity. The mechanism involves Abilify's effect on the dopamine receptor. Abilify will stimulate the dopamine receptor like a stimulant where dopamine is low and block the receptor like a mood stabilizer where dopamine is high. This is helpful in patients with combination ADHD plus Bipolar disorder. On the other hand, if the dose of Abilify is too high, it can worsen hyperactivity and cause a patient to feel restless and unable to sit still. Another rare and temporary side effect of abilify is called acute dystonic reaction. This side effect will go away on its own once abilify is stopped. Acute dystonic reaction is when a muscle, usually in the face, eyes, mouth, or neck becomes "locked". For example the head can turn or the eyes can look up and the person can not change the direction the muscle has locked into. Usually, there is also intense pain with the locked muscle. If this occurs, take 50mg of Benadryl (dyphenhidramine) by mouth. If the locked muscle prevents you from being able to swallow, go to an emergency room to get a shot in the arm of benadryl or cogentin (benztropine). Either rout of getting the antidote in your body will resolve the symptoms in 15 minutes or less. The patient should also stop taking abilify and call the doctor. Seroquel is very helpful for bipolar disorder. Its pros are that it helps both manic and depressive phases of bipolar disorder. If a person has trouble sleeping, Seroquel is extremely helpful for sleep. Seroquel probably has the lowest risk of tardive dyskanesia in this group. It does not cause restlessness at higher doses. The negatives are higher rates of sedation, increased levels of cholesterol and lipids, and likely higher risk of diabetis then some of the others in this group, although not for certain. Risperdal (risperidal) is the first widely prescribed second generation antipsychotic. Thus, a strong positive is that it has the most research done on it and we know more about it than the others in this group. There are less unknowns about this medication. It works well for psychosis, and it also helps with mania and likely helps with depression but has no FDA approval for this. Risperdal is generic thus it is the least expensive. Risperdal is uniquely beneficial for patients with autism and is FDA approved for the treatment of behavioral problems associated with Autism. Risperdal's negatives are as follows. It often causes weight gain and daytime sedation. It has a risk of tardive dyskenisia. It has a similar to slightly less risk of diabetis as seroquel. It greatly increases prolactin. Usually this does not cause any apparent difficulties and requires no action. Prolactin is a hormone secreted by the pituitary gland at the base of the brain. It stimulates breasts to secrete milk in nursing mothers. I am unsure what effect a four fold increase in prolactin does to a person. Very rare symptoms of increasedprolactin include lower sexual functioning, breast development in boys or girls, and unknown risks of activating tumor cell growth. A newer form of Risperdal called Invega has recently been released. It has a similar profile to Risperdal but is more expensive than Risperdal The above side effects can be serious but are extremely rare. Because risperdal has been around a while and has been shown to be safe in children and adults, it is often the first choice of many psychiatrists for their patients. The last medication in the group is Zyrexa. It is a newer form of the medication clozapine (Clozaril). Clozapine has a risk of agranulocytosis that requires weekly to monthly blood draws for the entirety of one taking the medication. It, however has been shown in study after study to work the best. On the other hand, it also has other serious side effects that preclude it from being used except in the most treatment resistant cases. Because Zyprexa is similar, it retains some of clozapine's pros and cons. Zyprexa probably works a little better than the other antipsychotics. But it probably has the greatest weight gain and increase in cholesterol. It is mildly to moderately sedative in the daytime. While it is completely undecided at this time, my own medical opinion is that Zyprexa probably has a slightly higher risk of diabetis than most of the other meds in this group. But I strongly reiterate, this is not a settled issue and more information is still needed to say for sure, one way or the other. Tardive dyskenisia is also a risk with Zyprexa. |
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