Pine Rest Mission Statement
Pine Rest Christian Mental Health Services is called to express the healing ministry of Jesus Christ by providing behavioral health services with professional excellence, Christian integrity and compassion.

Medications Used in the Management of Bipolar Spectrum Disorders

By Kevin M. Furmaga, Pharm.D., BCPP

INTRODUCTION
The first recognized medication treatment for bipolar symptoms emerged in 1949 with the lithium carbonate could be used safely to control mania. Since 1972, this simple mineral has been the gold standard to which all other antimanic agents are compared. Psychiatry has witnessed a recent expansion in the number of medications available to manage the complex and varied symptoms that can occur during an episode of bipolar mania or bipolar depression. However, no single drug effectively controls all symptoms or stabilizes all phases of this chronic illness. Successful treatment of bipolar disorder usually requires that two or more medications be prescribed at the same time. Close symptom monitoring with frequent adjustment in the type and dose of medications may be necessary to achieve long-term mood stability. This article will help familiarize you with the medications available to manage bipolar symptoms and review steps persons with this illness can take to meet the therapeutic challenge..

THE FOUNDATION OF DRUG THERAPY FOR BIPOLAR SPECTRUM DISORDERS

ANTIMANIC AGENTS (MOOD STABILIZERS)
Antimanic medications are essential for the treatment of bipolar disorder. Not only do they treat manic symptoms, they can reduce the risk of recurrent manic episodes, enhance antidepressant effects, and increase the safety of antidepressant treatment by preventing antidepressant-induced mania. FDA-approved and off-label medications for the treatment of mania can be divided into three groups: 1) Lithium Salts, 2) Anticonvulsants, and 3) New-Generation Antipsychotics

Lithium Salts
Lithium carbonate and lithium citrate are salts of lithium that come in a variety of immediate-release and extended-release oral products. These first-line medications are prescribed for the treatment of active mania symptoms and useful either alone or in combination with an antidepressant for treating both bipolar and unipolar depression. Lithium salts are also effective for preventing episodes of both mania and depression. Therapeutic drug monitoring is standard when lithium salts are prescribed. This involves routine monitoring of lithium blood levels and blood tests to check kidney function, thyroid function, and blood electrolyte balance.

Mood-stabilizing anticonvulsants
Some medications originally used to treat epilepsy are also used in the management of bipolar disorder.

This applies to valproic acid and carbamazepine, medications that not only treat seizures, but are FDA-approved for treating mania and mixed episodes of mania and depression. The most commonly prescribed formulation of valproic acid is the prodrug, divalproex sodium. Marketed under the brand names Depakote® and Depakote ER®, divalproex is converted to valproic acid. There are a number of brand name formulations of carbamazepine (see table on page 12), with Equetro® being approved for treating mania and mixed episodes of mania and depression. Regardless of the formulation used, the different brands of valproic acid or carbamazepine are equally effective as long as therapeutic blood levels are reached. Monitoring of blood levels, blood tests for liver function, and blood cell counts are routinely used to optimize the safe use and effectiveness of valproic acid and carbamazepine.

Lamotragine (Lamictal®) is FDA approved for use in patients with bipolar disorder to prevent recurrent episodes of depression. Unlike some antidepressants, lamotragine does not trigger episodes of mania. Its usefulness in treating active symptoms of depression is limited by the safety requirement that the dosage be increased slowly (6 – 8 weeks to reach a therapeutic dose). Rapid increases in dosage can lead to a serious allergic reaction called Stevens-Johnson Syndrome.

Oxcarbazapine (Trileptal®) and topiramate (Topamax®) are anticonvulsants used in bipolar disorder but at this time are not FDA-approved for this indication. Oxcarbazapine is similar to carbamazepine and a few clinical studies support its effectiveness in treating manic symptoms. It does not require therapeutic monitoring like carbamazepine and is overall better tolerated. Current evidence supporting the use of topiramate in bipolar disorder is very limited. It can sometimes prevent weight gain associated with other bipolar medications, which is another reason topiramate is prescribed as part of mood stabilizing regimens. Both Trileptal and Topamax are considered second line bipolar medications and should not be used unless first line medications fail or are not tolerated due to side effects.

New Generation Antipsychotics (NGAs)
Before they received FDA approval for treating manic symptoms, newer antipsychotics were used to treat psychotic illnesses like schizophrenia. Since the drugs in this antipsychotic subgroup also treat manic symptoms, they are sometimes referred to as broad spectrum psychotropics. Psychosis is not uncommon during episodes of bipolar mania or bipolar depression so these agents are particularly helpful for mania when psychotic symptoms are also present. New generation antipsychotics are often combined with mood-stabilizing anticonvulsants or lithium salts to better manage mania or combined with antidepressants to treat depression (and reduce the risk of antidepressant-induced mania). While they have a lower risk of causing the movement side effects (e.g., tremor, rigidity, slowed movements) commonly associated with older antipsychotics, safety concerns with NGAs center on their potential metabolic effects. An increased risk for weight gain, elevation in blood cholesterol and triglycerides, and diabetes requires monitoring in patients treated with this class of antimanic medication.

ANTIDEPRESSANTS
Antidepressants are used to treat bipolar depression, but patients with bipolar disorder should watch for early signs of mania after treatment with an antidepressant is started. Certain antidepressants appear to be more likely to trigger manic episodes than others. Older tricyclic antidepressants (e.g., Elavil®, Pamelor®), the dualacting antidepressants Effexor XR® and Cymbalta®, and Remeron® appear to increase the risk of mania in patients with a bipolar illness. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants, bupropion products (Wellbutrin®, Wellbutrin SR®, and Wellbutrin XR®) and nefazadone (formerly marketed under the brand name, Serzone) appear to have a lower risk for causing antidepressant-induced mania. To reduce the risk of mania with antidepressant treatment, an antimanic agent is also prescribed. Moodstabilizing lithium salts, anticonvulsants, or antipsychotics are all used for this purpose. The brand name medication, Symbyax®, is a combination of the mood stabilizing antipsychotic, olanzapine (Zyprexa®), and the antidepressant, fluoxetine (Prozac®).

ANXIOLYTICS (ANTI-ANXIETY MEDICATIONS)
Medications from the benzodiazepine class are often prescribed for bipolar treatment to target anxiety, agitation and restlessness, as well as insomnia. They are prescribed on either an “as needed” basis or a regular schedule to help manage symptoms over days or weeks. While medications like Ativan®, Klonopin®, Xanax®, and Valium® work within 30 minutes for selected symptoms, tolerance can develop to their therapeutic effects and they can be habit-forming. Given the high incidence of alcohol and other substance abuse in people with bipolar disorder, this is not a class of medication that can be prescribed safely in everyone with a bipolar diagnosis.

People with bipolar disorder should expect their medications to treat and prevent mood symptoms. Currently available medications can effectively manage bipolar symptoms, making full and productive lives possible. Longterm mood stability is likely when people with bipolar disorder are knowledgeable about the medications they are prescribed, report manic and depression symptoms to their doctor early, and recognize periodic adjustment in dose and change in medication may be necessary.

(Excerpted from "Today" magazine's "The Ups and Downs of Bipolar Disorder" issue. The complete article is available online at: http://www.pinerest.org/education/today/bipolar/default.asp)

Kevin M. Furmaga, Pharm. D., BCPP is a Board Certified Psychiatric Pharmacist and has served, since 1998 as a psychopharmacology consultant at Pine Rest Christian Mental Health Services/Saint Mary’s Health Care in Grand Rapids, Michigan. He is also an Adjunct Assistant Professor in the Department of Psychiatry at Michigan State University College of Human Medicine and in the Colleges of Pharmacy at the University of Michigan and Ferris State University. Dr. Furmaga is an accomplished clinician and clinical researcher. He has authored a number of journal publications and book chapters that focus on the pharmacologic management of psychiatric and neuropsychiatric disorders.

Bipolar Disorders: Torn Two Ways

By Carey A. Krause, D.O.

It has not been a good year for John. He was so excited as he started college last fall, but within weeks, trouble developed. He started missing classes. On several occasions his roommate found him in bed, shades drawn, in the middle of the day. Despite this, he was sleeping less; he could not shut down the anxious, ruminative thoughts in his brain. He stopped playing basketball and guitar, formerly his passions. He could not concentrate on homework, and he quickly fell behind in classes. By late October, he felt like a failure. Every waking moment was bleak, and the thought of being anywhere else, even nowhere, seemed preferable.

Fortunately, he made it to his family doctor, who quickly recognized the symptoms of depression, and had John start an antidepressant medication. Within three weeks he felt much better, and was able to salvage some of his classes, and defer the rest.

By spring though, something completely different happened to him. At first, his friends were thrilled to see how lively and talkative John had become. But they soon tired of his intrusiveness, and his flood of constantly changing ideas. Then he dropped out of school completely. He said he was starting his own business, and would be rich within a year. As if he already had the money, his first “business” purchase was a sports car. When his parents finally tracked him down, he was living in an empty storefront, and looked as if he hadn’t slept in a week. He talked non-stop on the way to the psychiatric hospital. When he realized where they were taking him, he accused his parents of being "corporate spies," and tried to jump out of the car.

The psychiatrist told John’s parents that he had a classic presentation of “bipolar I disorder.” She assured them that with medication, John would most likely be back to near-normal within weeks. For his parents, though, this was less than reassuring. What on earth had happened to their son, and what would prevent it from happening again?

WHAT IS BIPOLAR DISORDER?
Like most diagnoses in behavioral health, bipolar disorder (formerly known as manic-depression) is a diagnosis based on symptoms. In other words, physicians are not sure exactly what goes wrong in the brain to cause bipolar disorder, but they have seen the signs and symptoms often enough to be sure that it does represent a definite illness, or cluster of illnesses. At first, John exhibited signs of depression, including a lack of interest, concentration difficulty, sleep difficulty, and an overwhelming sense of hopelessness. His family doctor deserves credit for getting him started on antidepressants as soon as he was seen. But as is the case with at least 10 percent of those initially diagnosed with depression, it was the first warning of a bipolar disorder. Within weeks, he was starting to exhibit many of the symptoms of mania. His thoughts were racing from subject to subject. He began taking unacceptable risks and he believed he needed less and less sleep. He started developing grandiose beliefs about himself, which easily morphed into paranoid thoughts about everyone else.

Over their lifetime, about one to two percent of the population will develop bipolar symptoms as severe as John’s. To some extent, it is an inherited disease: one’s risk jumps from one percent to 15 percent if a close family member has bipolar illness. For some, the initial presentation is an episode of major depression. Within a few years, occasionally as quickly as within a few months, these individuals will cycle into an episode of mania, and the diagnosis will become obvious. Without proper treatment, though, they are destined to repeat the episodes in succeeding years. Many may have mostly depressed episodes while others may have repeated manic episodes. Left untreated, the episodes will become worse, and occur more frequently, leaving that individual’s entire existence in shambles. At least 60 percent of those with bipolar illness abuse alcohol or street drugs, often in an attempt to “self-medicate” the symptoms. The lifetime risk of suicide is as high as for any other psychiatric illness. Even with treatment, it approaches 15 percent of those affected.

TREATING BIPOLAR DISORDER
John’s psychiatrist started him on lithium, the first medication noted to be effective for treatment of bipolar disorders, and still the standard by which other medications are measured. Within a few days, he was talking less and listening more, and his intrusive behavior had improved. Lithium is one of the simplest of elements, and its effectiveness as a treatment for bipolar disorder continues to fascinate scientists. They have identified its role in changing the rate at which neurons create new proteins and operate internal chemical pathways, but it is a mystery as to how this leads to improvement of behavior.

In addition to lithium, physicians have identified a handful of drugs, initially introduced to control epileptic seizures that are often as effective as lithium in controlling bipolar behavior extremes. These include valproic acid (commonly known by the brand name Depakote), carbamazepine, and lamotrigine. The latter may be particularly beneficial in treating bipolar II disorder. It will be vital for John to understand that lithium is his ticket to ongoing stability. He will need to plan to take this medication for the foreseeable future, even when his symptoms are fully controlled, to minimize the risk of a future manic or depressive episode. In addition to the lithium, John’s doctor also prescribed an “atypical” antipsychotic medication. The antipsychotic quickly reduced John’s paranoid and grandiose thoughts, and he was able to recognize the need to agree to ongoing treatment. The atypical antipsychotic medications have become an important part of treating severe bipolar episodes. There is evidence they may also be useful long term to maintain stability.

Finally, John’s antidepressant medication was stopped, but his psychiatrist would not want the family doctor to think it had been a mistake to prescribe it for John’s depression. There is evidence that antidepressants, especially the older tricyclic antidepressants, can push a depressed bipolar patient into an episode of mania. However, a bipolar patient’s depression must still be treated. An individual suffering from a bipolar II illness is over 30 times more likely to suffer a repeat depression episode than an episode of hypomania. For them, timely use of an antidepressant may be life-saving. John’s psychiatrist will watch closely for depressive episodes in the future. She may treat them with an antidepressant, but will stop the antidepressant once symptoms have improved, to lessen the risk of a manic overshoot.

Medications used to treat bipolar disorder have risks associated with them, and John’s doctor will carefully go over those with him. With long term use, lithium can affect kidney and thyroid function, so those will be periodically monitored with blood tests in the future. Valproic acid can cause weight gain, and has (very rarely) been associated with liver inflammation or pancreatitis, which also means periodic laboratory monitoring is appropriate. In addition to the slight but ever-present risk of developing involuntary muscle movements, all of the atypical antipsychotics have been implicated in causing increases in blood sugar and blood lipid levels, which requires even more monitoring.

SOME FINAL THOUGHTS
Throughout history, physicians have recognized that a distinct group of their patients suffered from this unique illness of repeated manic or depressed spells. Arataeus wrote about the illness almost two thousand years ago in Alexandria. In the mid-nineteenth century, French physicians debated the origin of “circular insanity.” In our time, we continue to search for the “lesions” within the brain and the mistakes in our genes that lead to this severe and potentially disabling disorder. In the meantime, we fight to get effective treatments to sufferers, and to get them to stay in treatment.

I will sometimes tell my patients that a bipolar illness is the most severe illness of the brain one can have and still potentially lead a “normal” life. Indeed, several famous individuals have led remarkable lives while suffering from a bipolar disorder, and some have written about their trials. Kay Redfield Jamison, a psychologist at Johns Hopkins University, has written about her own struggle with bipolar illness in her memoir, An Unquiet Mind. Young authors, such as Lizzie Simon and Andy Behrman, have written contemporary accounts of their own illnesses. All tell of struggles and disappointments, but the fact that each has reached the point where they could write about their illness and have their manuscript published speaks to the potential for leading a productive life.

I predict success for our imaginary patient John. Hopefully the same is true for all of the very real individuals who are suffering from some form of a bipolar illness today. Fortunately, we have effective treatments, even as we struggle to understand the nature of the disease. Ultimately, the prescription is straightforward: stick with treatment, keep those appointments. The future is full of hope.

(Excerpted from "Today" magazine's "The Ups and Downs of Bipolar Disorder" issue. The complete article is available online at: http://www.pinerest.org/education/today/bipolar/default.asp)

Dr. Carey A. Krause received a Doctor of Osteopathy degree from Oklahoma State University College of Osteopathic Medicine and completed his residency at Michigan State University in psychiatric and internal medicine. He is Service Chief of Pine Rest’s Adult Inpatient Staff Psychiatrist at Pine Rest City Clinic. Dr. Krause also serves as Psychiatry Clerkship MSU Colleges of Human and Osteopathic Medicine.

March 3, 10, 17
Pine Rest Family Institute 'Secrets for Successful Marriage'
Pre-marital workshop taught by experienced marriage professionals for couples who want to grow their relationship in preparation for marriage. Because it is skill-based, it is a valuable addition to traditional pastoral or professional premarital counseling. 9 a.m. to noon. Cost: $95/couple. Call 616/455-5279 for more information.
For more information click here.

March 28
Institute for Spiritual Care Lecture Series
"Working with Spiritual Themes in Psychotherapy." The lecture will be held from 9 a.m. to 12:00 p.m.
This presentation will help participants explore definitions of spirituality to clarify its place in the therapy process. Multi-dimensional models will be introduced that can be used in a therapist’s model of care. Several approaches to spiritual themes in the community of practice will be reviewed and, using case examples, describe how therapists may approach spiritual themes with clients who are not religious.

PLEASE NOTE NEW LOCATION:
The Pinnacle Center
3330 Highland Drive
Hudsonville, MI 49426
For more information click here.

April 5, 2007
National Alcohol Screening Day
Pine Rest will be hosting this annual community service event at several outpatient clinics. Receive a free, confidential screening to learn if you or a loved one are experiencing problems with alcohol and, if so, how you can get help. The screening process includes a written self-test and the opportunity to meet with a trained health professional. Educational information also provided.
For more information click here.

April 25, 2007
Brain-Based Treatment Approaches for ADHD Across the Lifespan
Featuring Kathleen G. Nadeau, Ph.D., from 9 a.m. to 12:15 p.m. in the Pinnacle Center, 3330 Highland Drive, Hudsonville, MI. The lecture is free of charge and open to the public. For more information, call (616) 455-6500. 3 CME/CEU credits. 3 NASW CE clock hours.

Kathleen G. Nadeau, is Director for Chesapeake ADHD Center in Maryland. In addition, she is also Co-Founder and Chair for the National Center for Gender Issues and AD/HD (NCGI). Nadeau has lectured at numerous events including the 2005 ADHD Awareness Day in Boston, MA, and the 2005 SALT Conference held at the University of Arizona. She received a Ph.D. in psychology from the University of Florida.
For more information click here.

March 1, 8, 15, 22, 29
Eating Disorders Educational/Support Group
Pine Rest Christian Mental Health Services’ Northeast Clinic will continue offering a free, confidential eating disorders educational support group. This group is geared for persons with diagnosed eating disorders who are also receiving treatment from a health professional.

Facilitated by Michelle Muenzenmeyer, MA, LLP, this ongoing group meets every Thursday from 6:00 to 7:30 p.m. at the Northeast Clinic, 1700 East Beltline, NE, Suite 240.

An assessment or referral is required prior to joining the group. To schedule an assessment or for more information, interested persons should call Pine Rest’s Northeast Clinic at 616/364-1500.

Michelle Muenzenmeyer, MA, LLP, received a master’s degree in counseling psychology from Western Michigan University. She provides outpatient counseling to adolescents and adults, including individual and group therapy. She specializes in treating persons who have an eating disorder.
For more information click here.

March 12, April 9, May 14, June 11
Pine Rest’s Southwest Clinic To Host 'Family Connection' Support Group
"Family Connection" helps spouses, parents, siblings and other caregivers more effectively deal with the stresses created by the symptoms or behaviors associated with mental illness. The support group offers guidance through shared experiences, sharing effective coping strategies, and gaining knowledge about various disorders in a safe and confidential setting.

This ongoing group will meet the second Monday of every month from 5:30-6:30 pm at the clinic, located at 4211 Parkway Place, Suite # 100, Grandville (old 44th Street between Wilson and Canal). Jim VanderMay, LMSW, will facilitate the group.

To register, interested persons should contact the Southwest Clinic at (616) 222-3700, or fax (616) 222-3707 with name and the number of family members attending the meeting. Because of a grant from the Pine Rest Foundation, there will be no charge for attending the meetings.
For more information click here.

April 5, 12, 19, 26
Eating Disorders Educational/Support Group
Pine Rest Christian Mental Health Services’ Northeast Clinic will continue offering a free, confidential eating disorders educational support group. This group is geared for persons with diagnosed eating disorders who are also receiving treatment from a health professional.

Facilitated by Michelle Muenzenmeyer, MA, LLP, this ongoing group meets every Thursday from 6:00 to 7:30 p.m. at the Northeast Clinic, 1700 East Beltline, NE, Suite 240.

An assessment or referral is required prior to joining the group. To schedule an assessment or for more information, interested persons should call Pine Rest’s Northeast Clinic at 616/364-1500.

Michelle Muenzenmeyer, MA, LLP, received a master’s degree in counseling psychology from Western Michigan University. She provides outpatient counseling to adolescents and adults, including individual and group therapy. She specializes in treating persons who have an eating disorder.
For more information click here.

April 9
Pine Rest Family Connections Support Group
Monthly group for families who have a member with a diagnosed mental illness. Helps spouses, parents, siblings, and other caregivers more effectively deal with stress created by symptoms and behaviors. 5:30 – 6:30 p.m. at Pine Rest's Southwest Clinic, 4211 Parkway Place, Suite 100, Grandville. Cost: Free. Facilitated by Jim Vander May, LMSW. Call 616/222-3700, ext. 4 for more information.
For more information click here.

March 6, 13, 20, 27
Anger Management Classes for Adults
Led by Jim Bottenhorn, MA, LLP, Director of Pine Rest’s Contact Center. 7 p.m. to 8:30 p.m. on Pine Rest's main campus, 300 68th Street, SE, Grand Rapids. Open to adults and older teens. Registration is required. Cost: $65/individual or $95/two family members. Class fee due at first class. Call 616/493-6033 for more information and to register.
For more information click here.

March 6, 13, 20, 27
Anger Management For Teens
Led by Ryan LaRue, MSW, LMSW, ACSW, outpatient therapist at Pine Rest Campus Clinic. 4:15 -5:30 p.m. in the Van Andel Center on Pine Rest's main campus, 300 68th Street, SE, Grand Rapids. Open to male and female teens ages 12-17. Cost: $75/person. Call 616/222-4584 for more information or to register.
For more information click here.

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Copyright © 2007, Pine Rest Christian Mental Health Services. All rights reserved. The contents of Mental Health News & Information are for informational purposes only. The content is not intended to be a substitute for professional medical or mental health advice, diagnosis, or treatment. It cannot and should not be used as a basis for diagnosis or choice of treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical or mental health condition.