The Treatment of Bipolar Disorder

The treatment of bipolar disorder can be a daunting task. Not all types of bipolar disorder are alike just like not all patients are alike. What works for one patient may not work for another. While there is no cure for bipolar disorder, there are numerous medications available to assist a patient in leading a normal life. In addition to medications, psychotherapy is often utilized in conjunction with medications.

Bipolar disorder consists of different cycles. The two main cycles are depression and mania. The degree to which a patient experiences these two factors can differ greatly. Also, while most patients experience cycles which are long in length, there are some patients who are "rapid cyclers". Their cycles alternate from depression to mania in a short amount of time.

Since there are different moods associated with bipolar disorder, some medications alleviate symptoms of mania while others alleviate symptoms of depression. Different classes of drugs are used in treatment. The main types of drugs used are mood stabilizers, antidepressants, and antipsychotics.

Mood stabilizers have properties of both antidepressants and antimanics. They should treat both mania and depression and prevent the recurrence of symptoms (Young, Macritchie, Calabrese 2000). The majority of bipolar patients are treated with a type of mood stabilizer. Lithium, Valproate, Carbamazepine, and Lamotrigine are all examples of mood stabilizers.

John Cade first discovered lithium's therapeutic effects in the 1940's. Cade believed that mental illness, particularly manic-depressive illness, was caused by a biological factor. He set out to prove this by first looking at the urine composition of patients, thinking that there may be a toxin present. He wanted to inject the urine into guinea pigs but because urine itself is toxic, he needed to combine it with water to make it soluble. Uric acid is insoluble in water, but when combined with a lithium ion, it is soluble. Cade found that when the guinea pigs came into contact with the lithium, they were made lethargic and did not respond to stimuli (Mondimore 1999). Because of the desperation at the time for new treatment options, Cade was allowed to inject lithium carbonate into patients. Manic patients made a dramatic improvement. This was the first time lithium was used in treating a mental disorder.

Lithium has been shown to not only treat the manic cycle of bipolar disorder, but also to lessen the severity, duration, and frequency of manic and depressive episodes in patients (Mondimore 1999). In a comparison study of patients exhibiting a major depressive episode, lithium was shown to have an antidepressant response in 79% of the patients (Zornberg, Pope 1993). Lithium has a very narrow therapeutic range, meaning that there is a narrow margin between lithium being helpful to the patient and being toxic. Because of the risk of toxicity, blood levels must be drawn at least every three months. Also, a certain amount of lithium must be present in the bloodstream to be considered therapeutic.

Lithium does have side effects in some patients, which should be noted because of the risk of poor compliance from the patient. Some of its side effects include tremor, sedation, diarrhea, abdominal pain, indigestion, hypothyroidism and weight gain. These side effects are a major factor in non-compliance and have provoked many physicians into not prescribing it (Dinan 2002). If a patient decides to discontinue their lithium, there is a risk of recurrence of their symptoms. In one study, 50% of new episodes occurred within 10 weeks of discontinuation (Suppes 1992). In this study, the average time for half of the subjects to demonstrate a new episode was 5 months (Suppes 1992).

Maintenance therapy for bipolar disorder often includes lithium, but is usually of combination of one or more drugs. Lithium alone is not used as a treatment of the depression cycle (Shelton 2003).

Valproate, another mood stabilizer, is effective as an anti-manic drug. Like lithium, is seems to be effective in the prevention of recurrence of cycles (Mondimore 1999). In one study, using 179 hospitalized patients, it was determined that any depressive episodes that occurred in patients were directly associated with how well they responded to valproate. If the patient had a depressive episode, they responded more favorably to valproate than to lithium (Swann 1997). Valproate's side effects are not as common as lithium but do occur. Some of its side effects include stomach upset, sleepiness, and mild tremors. Because of its lower rate of side effects, valproate is rated the best-tolerated treatment for prevention of future episodes.

Valproate is currently the treatment of choice in rapid-cycling bipolar patients (Brigham 2003). Valproate can be used as a second-line treatment for those patients who do not respond well to lithium or experience significant side effects.

Carbamazepine is another mood stabilizer used effectively in patients who do not respond well to lithium. It came about in the 1960's and was used as an anticonvulsant for epilepsy. Several patients with epilepsy who had mood problems noticed not only an improvement for their seizure, but also for their moods (Mondimore 1999). There is evidence that carbamazepine is more effective in treating mania than in treating depression (Young, Macritchie, Calabrese 2000). The side effects of Carbamazepine are usually short-lived and include sleepiness, lightheadedness, and nausea. Blood levels need to be drawn to ensure that no liver problems are occurring.

Lamotrigine is also an anticonvulsant that can help episodes of bipolar disorder. While valproate and carbamazepine do not seem to help with the depressive episodes of bipolar disorder, there is evidence that lamotrigine has anti-depressive properties (Mondimore 1999). In one study, 70% of the patients involved responded favorably to Lamotrigine (Shelton 2003). In another study, lamotrigine was shown to improve the overall relapse rate of patients (Young, Macritchie, Calabrese 2000). Lamotrigine exhibits the same side effects as carbamazepine and has a much lower toxicity than lithium. Blood levels are not usually drawn because of this, making it less expensive than other mood stabilizers.

Olanzapine is another mood stabilizer that works on controlling manic episodes. The FDA has only approved it for use in the treatment of mania, however long term studies are showing it to be useful in mood stabilization as well (Brigham 2003). When it is used in combination with lithium or valproate, olanzapine provided more efficiency than when lithium or valproate is used alone. Weight gain is a major side effect of olanzapine and patients may stop taking it prematurely because of this.

Gabapentin is yet another anticonvulsant that may be useful to treat bipolar disorder. It is usually used in conjunction with another mood stabilizer and helps in reducing depressive episodes (Brigham 2003). A disadvantage to the drug is that it needs to be taken up to four times per day, which can interfere with patient compliance. Topiramate is also an anticonvulsant with mood stabilizing properties. It has been reported to cause depression is some patients (Brigham 2003). It is used as an adjunctive treatment usually with Valproate because it may counteract the weight gain associated with Valproate (Brigham 2003).

Antidepressants are used in the treatment of bipolar disorder, but almost never as a monotherapy. The reason being that an antidepressant alone can cause manic symptoms or an acceleration of the illness in some patients.

The most commonly used antidepressant groups are SSRI's and MAOI's. Trycyclics are not usually used because they can induce rapid cycling of the patient's symptoms (Griswold, Pessar 2000). Antidepressants are usually used as short-term therapy for a patient experiencing a major depressive episode. There is a debate going on in the psychiatric world regarding how effective long-term antidepressant therapy is and whether it is detrimental to the patient. Usually the patient is prescribed fluoxetine or bupropion for their depressive episode, but continue to take a mood stabilizer.

During manic episodes, patients sometimes become out of touch with reality or psychotic. It is estimated that between 50 and 75% of manic episodes include psychotic features (Sachs 2001). A mood stabilizer or antidepressant may take weeks to begin working, so an antipsychotic, or neuroleptic may be prescribed. 30-40% of patients in treatment for bipolar disorder are prescribed neuroleptics for long periods of time (Brigham 2003). Because of the risk of significant side effects such as tardive dyskinesia and seizure, it is suggested that neuroleptics only be used during the acute manic episode with psychotic features and not as long-term therapy. However, in one report 46% of all bipolar patients hospitalized continued to take an antipsychotic medication 4 years after discharge from the hospital (Kafantaris et al 2001). The neuroleptic should be discontinued gradually so that the psychosis does not reoccur.

Risperidone has a favorable response rate in bipolar patients experiencing psychotic episodes. In one study, the response rate was 70% (Brigham 2003). Risperidone is just one example of a neuroleptic used in treating bipolar patients.

Electroconvulsive therapy, ECT, is also used in cases with little response to mood stabilizers. ECT was first used in the 1940's to treat schizophrenia. It has been shown to help treat the symptoms of mood disorders including bipolar disorder (Vaidya, Mahableshwarkar, Shahid 2003). In one study, 80% of patients showed a marked clinical improvement with ECT (Mukherjee, Sackheim, Schnurr 1994). The frequency of treatments is recommended to be 3 times per week. ECT is not meant to be a first line treatment for the manic state of bipolar disorder, but is used for patients who are resistant to mood stabilizers and other treatments. In fact, in one study a comparison between using lithium and a antipsychotic alone versus ECT found that 59% of those receiving ECT had a complete remission. None who received combination therapy had remission (Fink 2001). It is also used in patients who are non compliant and/or suicidal. Because of the risk of suicide in patients undergoing a major depressive episode, ECT should be considered when a rapid response is needed to prevent harm to the patient. ECT is considered to be extremely safe, especially with today's standards of using anesthesia and muscle relaxants during administration.

Psychotherapy can be very helpful in managing bipolar disorder. Education, family intervention, mood charting, and counseling can be useful tools.

Education of the patient and their family about bipolar disorder is imperative. It is important for the patient to understand the exact nature of their illness, what kinds of treatments they should expect to receive, and what kind of outcomes they should expect. The patient should be made aware of their specific psychological stressors so that they may avoid severe episodes of mania. The patient's family should be involved because the patient can not always determine if they are entering an episode, while the people around them might have a greater appreciation of the circumstances. In a pilot study, patients involved in family therapy had greater improvements in family functioning, higher rates of full recovery, and lower rates of rehospitalizations for the 2 years following family therapy (American Psychiatric Association 2003).

Behavior Therapy involves scheduling daily activities, self-control therapy, training of social skills, and problem solving (American Psychiatric Association 2003). When combined with medications, behavior therapy seems to help especially with depressive episodes.

Mood charting is a particularly helpful tool for both the patient and their clinicians. The patient writes down their mood every day, and with the clinician's help, the patient can give a more objective opinion about what they feel might have caused a specific episode. Mood charting can also be helpful in giving an objective outlook for the medications taken. If a patient says that they do not feel a specific medication is working at all for them, the clinician and the patient can look at their mood charting and see if that is necessarily so. If their moods have gone up gradually from depressive state, the patient may not be able to tell, but the meticulous charting might shed some light on it.

In a personal interview I conducted, Jane Doe^* had been hospitalized in 1996 for attempted suicide. Although she had been in and out of therapy since the beginning of adolescence for depression, she was not diagnosed with bipolar disorder until her hospitalization. While an in-patient, she was taking lithium and Paxil (an anti-depressant). She engaged in group therapy while hospitalized, but expressed doubt that it helped her. Jane felt that one on one therapy would have been more beneficial to her. But, like we discussed in class, one on one therapy is very expensive in hospitalizations, and insurance did not cover it. She continued lithium therapy for approximately 3 years, but became depressed because of the weight gain she suffered during treatment. Her psychiatrist discontinued the lithium and prescribed valproate for her. Jane continues to take valproate, but no longer takes Paxil unless entering into a depressive episode. Jane continues to speak with a psychologist between once and twice a month. She regularly meets with a psychiatrist to discuss medications. When asked about manic or hypomanic episodes, Jane tells me that she has not had a major manic episode since before she was hospitalized. Jane explains that occasionally she will feel a certain sense of euphoria and have urges to go on spending sprees, but that through her psychotherapy and medications she can control these urges. She explains to me that before she was diagnosed she would have these same feelings, but be unable to control them. Jane feels very good with her progress in life and dealing with bipolar disorder. She is thankful that she has found the right kind of medications to help her treatment.

Jane Doe's experiences seem to support most of the research done on treatment for bipolar disorder. I was especially interested in her willingness to try a new mood stabilizer because of the side effects of lithium. It surprised me that patients feel so much better taking lithium but decide to try something new to see if they can be rid of the side effects. This reinforces the idea that many patients discontinue their medications because of side effects.

Most of the research done on the treatment of bipolar disorder focuses on medications. I read many articles about different clinical trials of monotherapy versus combinations of medications, but I could not find much information on recurrence rates or remission rates of patients taking medications and receiving psychotherapy. While medication is the cornerstone of treatment for this disorder, more research needs to be done on psychotherapeutic treatments, especially for the depressive episodes of this disorder.

In my research, I found that in this country there has been a significant backlash against lithium as a primary treatment option for bipolar disorder. But, in all the journal articles I read about lithium, most of the research states that lithium should still be the drug of choice for bipolar disorder except in patients who are resistant to it. In my interview with Jane Doe, she related to me how much she disliked having to get blood work-ups all of the time. She said that this point alone made her feel like she was chronically sick. It seems that more research needs to done to find a medication that is as effective as lithium, but causes very few side effects.

The anticonvulsant drugs present a new frontier for research on bipolar disorder. Most of the research I read found that these new drugs work better in conjunction with lithium or valproate and not as a monotherapy. Just the fact that they seem to have an effect at all is encouraging for treatment options.

It was surprising to me that ECT is so effective at treating bipolar disorder. All of the research I did pointed out that ECT is only used "when all else fails". If ECT can be effective in hard to treat cases, perhaps it could be more effective in other cases as well. More research should be done on whether the stigma attached to ECT is causing it to be utilized less than it should be. Patients should also be educated on how it is performed today, and how it may be more beneficial than they are aware.

There is much research going on right now to discover how and why some medications work for some patients and not for others. It must be extremely frustrating to a patient newly diagnosed with bipolar disorder to have to try different medications and wait for them to become effective. The patient in the meantime has to suffer through their symptoms. It will be amazing in the coming years for researchers to discover a brand new therapy that works for all patients.

While there are many different types of medications and therapies that exist today for the treatment of bipolar disorder, it is important to note that just as not all people are the same, not all illnesses are the same. At this time, bipolar disorder is not curable, but it is treatable. It may take time and effort on the part of the patient and their family, but eventually the right treatment will be found for them.

References

Brigham, Peter M. The Psychopharmacology of Bipolar Disorder. Retrieved April 21, 2003 from the World Wide Web: http://home.attbi.com/~pmbrig/BP_pharm.html.

Dinan, TG (2002). Lithium in bipolar mood disorder: evidence suggests that lithium should still be first choice for prophylactic treatment. British Medical Journal, v324 i7344. 989-991.

Fink M, Young A (2001). Treating bipolar affective disorder. British Medical Journal, v322 i7282. 365.

Griswold KS, Pessar LF. (2000). Management of Bipolar Disorder. American Family Physician, v62 i6, 1343.

Grof P (2002). Mood Disorders-New Definitions, Treatment Directions, and Understanding. Canadian Journal of Psychiatry, v47 i2. 123-125.

Kafantaris V, Coletti, DJ, Dicker R, Padula G, Kane J (2001). Adjunctive Antipsychotic Treatement of Adolescents with Bipolar Psychosis. Journal of the American Academy of child and Adolescent Psychiatry v40 i12. 1448-1457.

Mondimore, Francis Mark (1999). Bipolar Disorder: A Guide for Patients and Families. Baltimore: The Johns Hopkins University Press

Mukherjee S, Sackeim HA, Schnurr DB (1994). Electroconvulsive therapy of acute manic episodes: a review. American Journal of Psychiatry v151. 169-176.

Practice Guideline for the Treatment of Patients with Bipolar Disorder. American Psychiatric Association. Retrieved April 27, 2003 from the World Wide Web: http://www.psych.org/clin_res/pg_bipolar_2.cfm.

Sachs, GS (2001). A 25-Year-Old Woman with Bipolar Disorder. The Journal of the American Medical Association, v285 i4. 454.

Shelton, RC (2003). Treating bipolar depression: newly diagnosed patients may resist taking a mood stabilizer, but the cycling-not just the depression-requires treatment. Journal of Family Practice v52 i3. S14-S18.

Suppes, T (1992). Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. The Journal of the American Medical Association, v267 n15. 2022.

Swann, AC. (1997). Depression during mania: treatment response to lithium or divalproex. The Journal of the American Medical Association, v277 n13. 1017.

Vaidya NA, Mahableshwarkar AR, Shahid R (2003). Continuation and Maintenance ECT in Treatment-resistant Bipolar Disorder. Entrez PubMed.

Young AH., Macritchie KAN., Calabrese JR (2000). Treatment of bipolar affective disorder: new drug treatments are emerging, but more clinical evidence is required. British Medical Journal v321 i7272. 1302.

Zornberg GL, Pope HG Jr. (1993). Treatment of depression in bipolar disorder: new directions for research. Journal of Clinical Psychiatry,v13, 397-408.