Bipolar Pharmacological Treatments
Robbyn R. Wallace
Bipolar disorder is characterized by many symptoms that can be broken into manic and depressive episodes. The depressive episodes are characterized by intense feelings of sadness and despair that can become feelings of hopelessness and helplessness. Some of the symptoms of a depressive episode include anhedonia, disturbances in sleep and appetite, psychomotor retardation, loss of energy, feelings of worthlessness, guilt, difficulty thinking, indecision, and recurrent thoughts of death and suicide (Hollandsworth, Jr. 1990). The manic episodes are characterized by elevated, expansive or irritable mood, increased energy/hyperactivity, pressure of speech, flight of ideas, inflated self esteem, decreased need for sleep, poor judgment and insight, and often reckless or irresponsible behavior (Hollandsworth, Jr. 1990). Rarest symptoms were periods of loss of all interest and retardation or agitation (Weisman, 1991). Most commonly, individuals with manic episodes experience a period of depression. Bipolar disorder is diagnosed if an episode of mania occurs, whether depression has been diagnosed or not (Goodwin, Guze, 1989, p 11). Bipolar disorder affects approximately one percent of the population (approximately three million people) in the United States. As the National Depressive and Manic Depressive Association (MDMDA) have demonstrated, bipolar disorder can create substantial developmental delays, marital and family disruptions, occupational setbacks, and financial disasters. This devastating disease causes disruptions of families, loss of jobs and millions of dollars in cost to society. Many time’s bipolar patients report that the depressions are longer and increase in frequency as the individual ages. Often time's bipolar states and psychotic states are misdiagnosed as schizophrenia. Speech patterns help distinguish between the two disorders (Lish, 1994).
Table 1
Classification of Mood Disorders
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Bipolar disorder (a) Depressive disorder (b)
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Bipolar I Major depressive disorder
Manic episode Major depressive episode
Mixed episode Dysthymic disorder
Bipolar II Depressive disorder NOS
Hypomanic episode
Cyclothymic disorder
Bipolar disorder NOS
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Note. Categories are from the text revision of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 2000). Classification of mood disorders excludes those mood disorders that are due to a general medical condition or a substance. NOS _ not otherwise specified. (a) These disorders involve either depressive episodes or symptoms. (b) By definition, assigning a depressive disorder diagnosis indicates that there has never been a history of manic or hypomanic episodes or symptoms. (Rivas-Vazquez, Rey, Johnson, & Blais, 2002)
The onset of Bipolar disorder usually occurs between the ages of 20 and 30 years of age, with a second peak in the mid-forties for women. A typical bipolar patient may experience eight to ten episodes in their lifetime. However, those who have rapid cycling may experience more episodes of mania and depression that succeed each other without a period of remission (DSM III-R). The three stages of mania begin with hypomania, in which patients report that they are energetic, extroverted and assertive (Hirschfeld, 1995). The hypomania state has led observers to feel that bipolar patients are "addicted" to their mania. Hypomania progresses into mania and the transition is marked by loss of judgment (Hirschfeld, 1995). Often, euphoric grandiose characteristics are displayed, and paranoid or irritable characteristics begin to manifest. The third stage of mania is evident when the patient experiences delusions with often-paranoid themes. Speech is generally rapid and hyperactive behavior manifests sometimes associated with violence (Hirschfeld, 1995). When both manic and depressive symptoms occur at the same time it is called a mixed episode. Those afflicted are a special risk because there is a combination of hopelessness, agitation, and anxiety that makes them feel like they "could jump out of their skin"(Hirschfeld, 1995). Up to 50% of all patients with mania have a mixture of depressed moods. Patients’ report feeling dysphoric, depressed, and unhappy; yet, they exhibit the energy associated with mania. Rapid cycling mania is another presentation of bipolar disorder. Mania may be present with four or more distinct episodes within a 12-month period. There is now evidence to suggest that sometimes rapid cycling may be a transient manifestation of the bipolar disorder. This form of the disease exhibits more episodes of mania and depression than bipolar.
Table 2
Core Features of Mania and Hypomania
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1. Inflated self-esteem or grandiosity
2. Decreased need for sleep (e.g., feels rested after only 3 hr of sleep)
3. More talkative than usual or pressure to keep talking
4. Flight of ideas or subjective experience that thoughts are racing
5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
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Note. From the text revision of the Diagnostic and Statistical Manual for Mental Disorders (4th ed.; APA, 2000). (Rivas-Vazquez, Rey, Johnson, & Blais, 2002)
Lithium has been the primary treatment of bipolar disorder since its introduction in the 1960's. It is main function is to stabilize the cycling characteristic of bipolar disorder. In four controlled studies by F. K. Goodwin and K. R. Jamison, the overall response rate for bipolar subjects treated with Lithium was 78% (1990). Lithium is also the primary drug used for long- term maintenance of bipolar disorder. In a majority of bipolar patients, it lessens the duration, frequency, and severity of the episodes of both mania and depression. Unfortunately, as many as 40% of bipolar patients are either unresponsive to lithium or can not tolerate the side effects. Some of the side effects include thirst, weight gain, nausea, diarrhea, and edema. Patients who are unresponsive to lithium treatment are often those who experience dysphoric mania, mixed states, or rapid cycling bipolar disorder. One problem associated with lithium is the fact the long-term lithium treatment has been associated with decreased thyroid function in-patients with bipolar disorder. Preliminary evidence also suggest that hypothyroidism may actually lead to rapid cycling (Bauer et al., 1990).
There are other effective treatments for bipolar disorder that are used in cases where the patients cannot tolerate lithium or have been unresponsive to it in the past. The American Psychiatric Association's guidelines suggest the next line of treatment to be Anticonvulsant drugs such as valproate and lamotrigine. These drugs are useful as antimanic agents, especially in those patients with mixed states. Both of these medications can be used in combination with lithium or in combination with each other. Valproate is especially helpful for patients who are lithium noncompliant, experience rapid cycling, or have comorbid alcohol or drug abuse. Neuroleptics such as haloperidol or chlorpromazine have also been used to help stabilize manic patients who are highly agitated or psychotic. Use of these drugs is often necessary because the response to them is rapid, but there are risks involved in their use. Because of the often-severe side effects, Benzodiazepines are often used in their place. Benzodiazepines can achieve the same results as Neuroleptics for most patients in terms of rapid control of agitation and excitement, without the severe side effects. Some doctors as treatment for bipolar disorder have also used antidepressants such as the selective serotonin reuptake inhibitors (SSRI’s) fluovamine and amitriptyline. A double-blind study by M. Gasperini, F. Gatti, L. Bellini, R.Anniverno, and E. Smeraldi showed that fluvoxamine and amitriptyline are highly effective treatments for bipolar patients experiencing depressive episodes (1992). This study is controversial however, because conflicting research shows that SSRI’s and other antidepressants can actually precipitate manic episodes. Most doctors can see the usefulness of antidepressants when used in conjunction with mood stabilizing medications such as lithium.
Table 3
Beyond Lithiuma: Current Pharmacological Armamentarium for Bipolar Disorder
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Anticonvulsants Calcium channel blockers Atypical antipsychotics Benzodiazepines Antidepressants
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valproatea verapamil olanzapinea lorazepam bupropion
carbamazepine diltiazem risperidone clonazepam paroxetine
lamotrigine nifedipine clozapine fluoxetine
gabapentin nimodipine quetiapine citalopram
topiramate ziprasidone sertraline
tiagabine venlafaxine
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Note. Drug names: valproate (Depakote); carbamazepine (Tegretol); lamotrigine (Lamictal); gabapentin (Neurontin); topiramate (Topamax); tiagabine (Gabitril); verapamil (Calan); diltiazem (Cardizem); nifedipine (Procardia); nimodipine (Nimotop); olanzapine (Zyprexa); risperidone (Risperdal); clozapine (Clozaril); quetiapine (Seroquel); ziprasidone (Geodon); lorazepam (Ativan); clonazepam (Klonopin); bupropion (Wellbutrin); paroxetine (Paxil); fluoxetine (Prozac); citalopram (Celexa); sertraline (Zoloft); venlafaxine (Effexor). Approved by the Food and Drug Administration for the treatment of acute mania. (Rivas-Vazquez, Rey, Johnson, & Blais, 2002)
In addition to the mentioned pharmacological treatments of bipolar disorder, there are several other options available to bipolar patients, most of which are used in conjunction with medicine. One such treatment is light therapy. One study compared the response to light therapy of bipolar patients with that of unipolar patients. Patients were free of psychotropic and hypnotic medications for at least one month before treatment. Bipolar patients in this study showed an average of 90.3% improvement in their depressive symptoms, with no incidence of mania or hypomania. They all continued to use light therapy, and all showed a sustained positive response at a three-month follow-up (Hopkins and Gelenberg, 1994). Another study involved a four-week treatment of bright morning light treatment for patients with seasonal affective disorder and bipolar patients. This study found a statistically significant decrement in depressive symptoms, with the maximum antidepressant effect of light not being reached until week four (Baur, Kurtz, Rubin, and Markus, 1994). Hypomanic symptoms were experienced by 36% of bipolar patients in this study. Predominant hypomanic symptoms included racing thoughts, decreased sleep and irritability. Surprisingly, one-third of controls also developed symptoms such as those mentioned above. Regardless of the explanation of the emergence of hypomanic symptoms in undiagnosed controls, it is evident from this study that light treatment may be associated with the observed symptoms. Based on the results, careful professional monitoring during light treatment is necessary, even for those without a history of major mood disorders. Another popular treatment for bipolar disorder is electro-convulsive shock therapy. ECT is the preferred treatment for severely manic pregnant patients and patients who are homicidal, psychotic, catatonic, medically compromised, or severely suicidal. In one study, researchers found marked improvement in 78% of patients treated with ECT, compared to 62% of patients treated only with lithium and 37% of patients who received neither, ECT or lithium (Black et al., 1987). A final type of therapy is outpatient group psychotherapy. According to Dr. John Graves, spokesperson for The National Depressive and Manic Depressive Association has called attention to the value of support groups, and challenged mental health professionals to take a more serious look at group therapy for the bipolar population. Research shows that group participation may help increase lithium compliance, decrease denial regarding the illness, and increase awareness of both external and internal stress factors leading to manic and depressive episodes. Group therapy for patients with bipolar disorders responds to the need for support and reinforcement of medication management, and the need for education and support for the interpersonal difficulties that arise during the course of the disorder.
It is clear that in our society many people live with bipolar disorder; however, despite the abundance of people suffering from the disorder, we are still waiting for definite explanations for the causes and cure. The one fact of which we are painfully aware is that bipolar disorder severely undermines its’ victims ability to obtain and maintain social and occupational success. Because bipolar disorder has such debilitating symptoms, it is imperative that we remain vigilant in the quest for explanations of its causes and treatment.
Methods
Participants
Participants were 20 Bipolar I patients receiving outpatient treatment from South Mississippi Psychiatric Group, who agreed to participate in a longitudinal study of the pharmacotherapy of the course of illness. Patients had been diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria, and all had a history of at least one manic episode. All the patients in the clinic received a 3- to 4-hr diagnostic evaluation from at least one staff psychiatrist, who also obtained detailed information on prior psychiatric history and treatment, including dates of previous hospitalizations for bipolar disorder. Following evaluation, patients were referred for treatment, and all the bipolar patients in the present study were on medication and followed by a staff psychiatrist. A research staff member, a monitored patient’ clinical status on the basis of psychiatrists’ records. When patients achieved remission or best clinical state, they were recruited. After participants received a complete description of the study, written informed consent was obtained.
Procedure
An ongoing symptom assessment was used. Patients were seen on an as-needed basis by their psychiatrists (usually monthly, but varying by individual need from weekly to every 3 months). At each visit, the psychiatrist completed a DSM-IV checklist of symptoms, including those occurring since the last visit, of mania, hypomania, and major and minor depression; the psychiatrist also completed his case notes. Changes in symptoms were dated as carefully as possible. The physicians also made ratings of medication compliance and noted current medication treatment. The patient was blind to physician records including routine clinic procedures.
The information from patient visit reports were transferred by research staff to individual symptom time lines that indicated diagnostic status and dates and duration of symptoms. The research staff, to determine whether and when patients experienced a significant change over the course of the follow-up inspected the time lines. The time lines were also used to determine how many, if any, and how often relapses occurred during year 1; and also to determine how many remained in remission at the year 1 follow-up. The research staff inspected each patient’s records every 2 weeks for year 1. At each 2-week inspection of records, it was noted whether the patient remained in remission or had a relapse. Also, the inspection noted whether the patients’ medications had changed when relapse occurred. At the end of year 1 each patient’s records were reviewed by the research staff and analyzed for success of attaining remission status.
Results
Among the patients, 4 were full-time students, 2 were professionals, 6 were too disabled to work (although a few performed voluntary services), and the rest worked at least part-time on a regular basis. Overall, 60% remained in remission at the end of year 1; whereas, 40% were not in remission at the end of year 1. Patients who remained in remission with less than 2 relapses in year 1 consisted of 2 students and 2 professionals. Patients which remained in remission with 2 but less than 4 relapses in year 1 consisted of 2 students, 1 disabled, and 1 part-time worker. Patients who remained in remission at the end of year 1 with 5 or more relapses and at least one hospitalization consisted of 2 disabled and 2 part-time workers. Patients who were not in remission at the end of year 1 that were hospitalized 2 or more times consisted of 3 disabled and 5 part-time workers.
Conclusion
Students and professionals are more likely to have fewer relapses than disabled are and part-time workers are. Disabled and part-time workers are more likely to be hospitalized.
NOTE: -2 is remission with less than 2 relapses in year 1. +2 / -4 is remission with more than 2 but less than 4 relapses in year 1. +5 is remission with more than 5 relapses and at least one hospitalization is year 1. Hospital is not in remission with one or more hospitalizations in year 1.
Discussion
Diagnostic and treatments associated with bipolar disorder poses a challenge, particularly the various classes of medication currently used in pharmacotherapy for the disorder. (Rivas-Vazquez, Rey, Johnson, & Blais, 2002) This study was only to provide information on what type of patients attain remission versus not attaining remission. The results showed that students and professionals are the most successful at attaining remission with the least amount of relapses in year 1. They are more likely to be successful in remission because they are more educated. It shows that part-time workers are the most likely to not attain remission and to be hospitalized in year 1, with disabled patients coming in close second. Part-time workers may have a more difficult time reaching remission due to life-stress, such as social- or work-related. Disabled patients are usually monitored more closely with their medications, but are more prone to not take medications properly or stop taking medications, which can cause relapses. In all cases, it seems to be extremely important to have some type of therapy for support of medication therapy. A patient having had psychosocial interventions is more likely to attain remission. Although pharmacotherapy represents the primary treatment for bipolar disorder, augmentation with various psychotherapeutic techniques is now being recommended by practice guidelines (Rivas-Vazquez, Rey, Johnson, & Blais, 2002). To offset high rates of medication discontinuation and overall noncompliance, psychotherapy is becoming the primary target. Psychotherapeutic interventions are targeting risk factors associated with mood instability. (Rivas-Vazquez, Rey, Johnson, & Blais, 2002) Over the last several years, various forms of adjacent psychotherapy have been developed for bipolar disorder, including cognitive-behavioral, interpersonal, psycho-educational, and family therapies (Rivas-Vazquez, Rey, Johnson, & Blais, 2002). In this study we reviewed Bipolar disorder, diagnostic and pharmacological treatments, but did not review how psychotherapeutic interventions can impact the success of a patient to attain and maintain remission. The success rate is believed to be higher in-patients who receive psychotherapeutic interventions along with medications. Although lithium remains the most widely used resource, limitations associated with its use have prompted clinicians and researchers to explore the application of several different classes of agents, including anticonvulsants, calcium channel blockers, atypical antipsychotics, benxodiazepines and antidepressants, to the acute and long-term management of bipolar disorder. Psychotherapeutic modalities can serve as adjunctive interventions to pharmacotherapy. (Rivas-Vazquez, Rey, Johnson, & Blais, 2002)
References
Barlow, D. H., Durand, V. M. (2002). Abnormal Psychology: an integrative approach, 3rd ed. Canada: Wadsworth Group.
Bauer, M.S., Kurtz, J.W., Rubin, L.B., and Marcus, J.G. (1994). Mood and Behavioral effects of four-week light treatment in winter depressives and controls. Journal of Psychiatric Research. 28, 2: 135-145.
Bauer, M.S., Whybrow, P.C. and Winokur, A. (1990). Rapid Cycling Bipolar Affective Disorder: I. Association with grade I hypothyroidism. Archives of General Psychiatry. 47: 427-432.
Black, D.W., Winokur, G., and Nasrallah, A. (1987). Treatment of Mania: A naturalistic study of electroconvulsive therapy versus lithium in 438 patients. Journal of Clinical Psychiatry. 48: 132-139.
Gasperini, M., Gatti, F., Bellini, L., Anniverno, R., Smeralsi, E., (1992). Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. Pharmacopsychiatry. 26:186-192.
Goodwin, F.K., and Jamison, K.R. (1990). Manic Depressive Illness. New York: Oxford University Press.
Goodwin, Donald W. and Guze, Samuel B. (1989). Psychiatric Diagnosis. Fourth Ed. Oxford University. p.7.
Hirschfeld, R.M. (1995). Recent Developments in Clinical Aspects of Bipolar Disorder. The Decade of the Brain. National Alliance for the Mentally Ill. Winter. Vol. VI. Issue II.
Hollandsworth, James G. (1990). The Physiology of Psychological Disorders. Plenem Press. New York and London. P.111.
Hopkins, H.S. and Gelenberg, A.J. (1994). Treatment of Bipolar Disorder: How Far Have We Come? Psychopharmacology Bulletin. 30 (1): 27-38.
Jacobson, S.J., Jones, K., Ceolin, L., Kaur, P., Sahn, D., Donnerfeld, A.E., Rieder, M., Santelli, R., Smythe, J., Patuszuk, A., Einarson, T., and Koren, G., (1992). Prospective multicenter study of pregnancy outcome after lithium exposure during the first trimester. Laricet. 339: 530-533.
Lish, J.D., Dime-Meenan, S., Whybrow, P.C., Price, R.A. and Hirschfeld, R.M. (1994). The National Depressive and Manic Depressive Association (DMDA) Survey of Bipolar Members. Affective Disorders. 31: pp.281-294.
Rivas-Vazquez, R.A., Rey, G.J., Johnson, S.L., Blais, M.A. (2002). Professional Psychology: Research and Practice. 33, 2, 212-223.
Weisman, M.M., Livingston, B.M., Leaf, P.J., Florio, L.P., Holzer, C. (1991). Psychiatric Disorders in America. Affective Disorders. Free Press.
