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614-893-0910 or BTCarroll1@cs.com - 614-937-9427
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Information provided by: DBS Alliance.org
Symptoms of Bipolar Disorder Types of Bipolar Disorder
Treatments Bipolar Disorder in Children
Helping a friend Support Groups
Bipolar disorder (also known as manic depression) is a treatable illness marked by extreme changes in mood, thought, energy and behavior. It is not a character flaw or a sign of personal weakness. Bipolar disorder is also known as manic depression because a person’s mood can alternate between the "poles" mania (highs) and depression (lows). This change in mood or "mood swing" can last for hours, days weeks or months.
Bipolar disorder affects more than two million adult Americans. It usually begins in late adolescence (often appearing as depression during teen years) although it can start in early childhood or later in life. An equal number of men and women develop this illness (men tend to begin with a manic episode, women with a depressive episode) and it is found among all ages, races, ethnic groups and social classes. The illness tends to run in families and appears to have a genetic link. Like depression and other serious illnesses, bipolar disorder can also negatively affect spouses and partners, family members, friends and coworkers.
Symptoms of Bipolar Disorder
Bipolar disorder differs significantly from clinical depression, although the symptoms for the depressive phase of the illness are similar. Most people who have bipolar disorder talk about experiencing "highs" and "lows" – the highs are periods of mania, the lows periods of depression. These swings can be severe, ranging from extreme energy to deep despair. The severity of the mood swings and the way they disrupt normal life activities distinguish bipolar mood episodes from ordinary mood changes.
Symptoms of mania - the "highs" of bipolar disorder
Increased physical and mental activity and energy
Heightened mood, exaggerated optimism and self-confidence
Excessive irritability, aggressive behavior
Decreased need for sleep without experiencing fatigue
Grandiose delusions, inflated sense of self-importance
Racing speech, racing thoughts, flight of ideas
Impulsiveness, poor judgment, distractibility
Reckless behavior
In the most severe cases, delusions and hallucinations
Symptoms of depression - the "lows" of bipolar disorder
Prolonged sadness or unexplained crying spells
Significant changes in appetite and sleep patterns
Irritability, anger, worry, agitation, anxiety
Pessimism, indifference
Loss of energy, persistent lethargy
Feelings of guilt, worthlessness
Inability to concentrate, indecisiveness
Inability to take pleasure in former interests, social withdrawal
Unexplained aches and pains
Recurring thoughts of death or suicide
If you or someone you know has thoughts of death or suicide, contact a medical professional, clergy member, loved one, friend or hospital emergency room or call 911 immediately.
You cannot diagnose yourself. Only a properly trained health professional can determine if you have bipolar disorder.
Many people do not seek medical attention during periods of mania because they feel manic symptoms (increased energy, heightened mood, increased sexual drive, etc.) have a positive impact on them. However, left unchecked, these behaviors can have harmful results.
When symptoms of mania are left untreated, they can lead to illegal or life-threatening situations because mania often involves impaired judgment and reckless behavior. Manic behaviors vary from person to person. All symptoms should be discussed with your doctor.
Types of Bipolar Disorder
Patterns and severity of symptoms, or episodes, of highs and lows, determine different types of bipolar disorder.
Bipolar I disorder is characterized by one or more manic episodes or mixed episodes (symptoms of both a mania and a depression occurring nearly every day for at least 1 week) and one or more major depressive episodes. Bipolar I disorder is the most severe form of the illness marked by extreme manic episodes.
Bipolar II disorder is characterized by one or more depressive episodes accompanied by at least one hypomanic episode. Hypomanic episodes have symptoms similar to manic episodes but are less severe, but must be clearly different from a person’s non-depressed mood. For some, hypomanic episodes are not severe enough to cause notable problems in social activities or work. However, for others, they can be troublesome.
Cyclothymic disorder is characterized by chronic fluctuating moods involving periods of hypomania and depression. The periods of both depressive and hypomanic symptoms are shorter, less severe, and do not occur with regularity as experienced with bipolar II or I. However, these mood swings can impair social interactions and work. Many, but not all, people with cyclothymia develop a more severe form of bipolar illness.
There is also a form of the illness called bipolar disorder not otherwise specified (NOS) that does not fit in to one of the above definitions.
Because bipolar disorder is complex and can be difficult to diagnose, you should share all of your symptoms with your health care provider. If you feel your symptoms are not getting better with your current treatment and your doctor does not want to try something new, do not hesitate to see another doctor to get a second opinion.
Treatments for Bipolar Disorder
Several therapies exist for bipolar disorder and promising new treatments are currently under investigation. Because bipolar disorder can be difficult treat, it is highly recommended that you consult a psychiatrist or a general practitioner with experience in treating this illness. Your treatment may include medications and talk therapy.
Bipolar Disorder in Children
Bipolar disorder is more likely to affect the children of parents who have the disorder. When one parent has bipolar disorder, the risk to each child is estimated to be 15-30%. When both parents have bipolar disorder, the risk increases to 50-75%.
Symptoms of bipolar disorder may be difficult to recognize in children, as they can be mistaken for age-appropriate emotions and behaviors of children and adolescents. Symptoms of mania and depression may appear in a variety of behaviors. When manic, children and adolescents, in contrast to adults, are more likely to be irritable and prone to destructive outbursts than to be elated or euphoric. When depressed, there may be complaints of headaches, stomach aches, tiredness, poor performance in school, poor communication and extreme sensitivity to rejection or failure.
The treatment of bipolar disorder in children is based on experience in treating adults with the illness, since very few studies have been done of the effectiveness and safety of the medications in children and adolescents. It is important to find a doctor that is well-versed in treating this illness in children and one that you work closely with throughout the course of treatment.
According to the American Academy of Child and Adolescent Psychiatry, up to one-third of the 3.4 million children and adolescents with depression in the United States may actually be experiencing the early onset of bipolar disorder.
Helping a Friend
One of the most important thing family and friends can do for a person with bipolar disorder is learn about the illness. Often people who are depressed or experiencing mania or mood swings do not recognize the symptoms in themselves. If you are concerned about a friend or family member, help him or her get an appropriate diagnosis and treatment. This may involve helping the person to find a doctor or therapist and make their first appointment. You may also want to offer go with the person to their first appointment for support. Encourage the individual to stay with treatment. Keep reassuring the person that, with time and help, he or she will feel better.
It is also important to offer emotional support. This involves understanding, patience, affection, and encouragement. Engage the person in conversation and listen carefully. Resist the urge to function as a therapist or try to come up with answers to the person’s concerns. Often times we just want someone to listen. Do not put down feelings expressed, but point out realities and offer hope. Invite the depressed person for walks, outings, to the movies, and other activities. Be gently insistent if your first invitation is refused.
It is often a good idea for the person with bipolar disorder to develop a plan should he or she experience severe manic or depressive symptoms. Such a plan might include contacting the person’s doctor, taking control of credit cards and car keys or increasing contact with the person until the severe episode has passed. Your plan should be shared with a trusted family member and/or friend. Keep in mind, however, that people with bipolar disorder, like all people, have good and bad days. Being in a bad mood one day is not necessarily a sign of an upcoming severe episode.
Never ignore remarks about suicide. Report them to the person's therapist. Do not promise confidentiality if you believe someone is close to suicide. If you think immediate self-harm is possible, contact their doctor or dial 911 immediately. Make sure the person discusses these feelings with his or her doctor.
Support Groups
http://www.DBSAlliance.org
A special thank you to DBS Alliance for a wonderful resource for Bipolar patients.
ACUTE MANIA
ABSTRACT, By Brendan T. Carroll, M.D.
Treatment of acute mania has been greatly influenced by loading strategies. Loading has potential benefits including rapid symptom reduction in mania and a shortened length of stay. Disadvantages include an increased likelihood of adverse effects of these medications.
Loading strategies for lithium, valproic acid (i.e. divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, haloperidol decanoate and quetiapine in the treatment of acute mania will be discussed. Recent studies highlight this treatment option for selected patients. It is the unique properties of these medications that influence their use in loading. Issues in patient selection for these loading strategies with each of these medications will also be considered.
Pharmacological Loading Strategies:
Brendan T. Carroll, M.D.-2005
DEFINITIONS OF LOADING
The "loading dose" is one or a series of doses that may be given at the onset of therapy with the aim of achieving the target plasma concentration rapidly.3 Multiplying the target steady state plasma concentration (CSS ) by the Volume of Distribution (VD) gives the calculated loading dose (i.e. LD = CSS x VD).
A loading does may be desirable if the time required to attain steady state by a consistent rate (four elimination half-lives) is long relative to the temporal demands of the condition being treated. The use of a standard loading dose also has significant disadvantages. The particularly sensitive individual may be exposed abruptly to a toxic concentration of the drug. Moreover, if the drug involved has a long half-life it will take a long time for the concentration to fall if the level achieved was excessive. Loading doses tend to be large.3
A useful definition for loading is the administration of larger than usual doses of the medication to achieve the desired steady-state blood level (endpoint). Effective medications for the treatment of mania include lithium, valproic acid (i.e. divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, haloperidol and quetiapine.2 Loading strategies for each will be discussed.
Rapid Cycling:
Karen Tugrul, BS,RN. Prof. University of Cincinnati: She proposes that in order to properly diagnose the different degrees or stages in a bi-polar patient, a more comprehensive rating scale should be given to the patient at the initial onset. (for a copy of the rating scale, please send an e-mail to: BTCarroll1@cs.com) She remarks that a failure to get a true rating, particularly on a patient who has rapid cycling will not tell the true picture of the patient and if given anti-depressants, may trigger a manic episode. Ms. Tugrul was funded by a grant from The Neuroscience Alliance. We felt that this educational program was so important to the understanding of Bi-Polar patients, care givers and benefits physicians to get a more accurate picture as to where,(in the broad spectrum of Bi-Polar) a particular patient's illness is, at that particular time.
- Tressa Carroll, Neuroscience Alliance- 2005
What is Rapid Cycling?
-AltHealth U.K. 04/2005
Rapid cycling is defined as four or more manic, hypomanic, or depressive episodes in any 12-month period. Depressive episodes last two weeks or longer; hypomanic episodes last four days or longer; manic episodes last one week or longer or require hospitalization. However, episodes may be much more frequent and shorter.
While the term "rapid cycling" may lead some people to believe the episodes occur in cycles, they often follow a random pattern. Some patients with rapid cycling appear to experience true manic, mild manic, or depressive episodes that last only for a day. Typically, however, someone who experiences such short mood swings (ultrarapid cycling) has undergone longer episodes as well.
There is an indistinct boundary between rapid cycling and mixed states. Most physicians, however, believe that mixed-state bipolar disorder is distinct from rapid cycling, and do not diagnose rapid cycling unless full-length mood episodes take place.
For some people, rapid cycling is a temporary occurrence. That is, they may experience rapid cycling for a time, then return to a pattern of longer, less frequent episodes. Others, however, may continue in a rapid-cycling pattern indefinitely.
Who Develops Rapid Cycling?
As many as 15-20% of all individuals with bipolar disorder may develop rapid cycling at some time during their illness. Individuals with Bipolar I (those with manic or mixed episodes alternating with major depression) and Bipolar II (those with recurrent major depressive episodes and hypomania) have equal rates of rapid cycling. While there are no absolute rules about who will develop this pattern, up to 90% are women, despite bipolar disorder generally being equally common in both sexes. Several studies have also shown that rapid cycling occurs more frequently in people with bipolar disorder who have evidence of, or history of, hypothyroidism.
Use of antidepressants in bipolar disorder can bring on or worsen rapid cycling, although the cycling often decreases when the antidepressants are discontinued. Therefore, physicians should prescribe antidepressants cautiously.
There may also be a genetic or other physical link between rapid cycling and drug or alcohol abuse. Some studies show that substance abuse is more common in families of those with rapid-cycling bipolar illness than in families of bipolar patients without rapid cycling. Furthermore, a history of substance abuse may make an individual more prone to cycling with episodes that are sorter than usual.
When rapid cycling starts, it typically follows one of these patterns:
Some individuals experience rapid cycling at the beginning of their illness for others, onset is gradual. Most individuals with bipolar disorder, in fact, experience shorter and more frequent episodes as the illness progresses. Eventually, they may meet criteria for rapid cycling, either temporarily or permanently.
What Causes Rapid Cycling?
Courtesy of AltHealth U.K. Depression
Overview of Bipolar Disorder and Its Symptoms
04/2005
The fundamental cause of rapid cycling remains unknown, but three overlapping theories exist:
Kindling (Sensitization). According to this theory, episodes are initially triggered by actual or anticipated life events such as the death of a loved one or an upcoming job interview. As the sequence is repeated, however, the affected individual becomes increasingly sensitive to anything that may be a trigger. Episodes become increasingly frequent and independent of anything outside the patient's brain. Sometimes, the result of this process may be rapid cycling.
Biological Rhythm Disturbances. This theory proposes rapid-cycling patients' daily biological rhythms are abnormal and out of sync with typical "time-giving" events such as dawn and dusk. This theory could then account for the sleep disturbances typical of mania and depression and explain other symptoms as well. If biological rhythms are important, a link between rapid cycling and seasonal affective disorder (SAD) may be suggested. SAD is a type of depression that typically develops during the fall and winter months and lessens in intensity or completely subsides during the summer months.
Hypothyroidism - This theory proposes that rapid cycling is due to inadequate amounts of thyroid hormone in the brain. However, most people with rapid cycling have adequate blood levels of thyroid hormone. Nevertheless, low blood levels of thyroid hormone are more common among individuals with rapid cycling than among bipolar patients in general. For this reason, thyroid function tests should be carried out before and during treatment.
Are There Effective Treatments for Rapid Cycling?
While 60% of other individuals with bipolar disorder will obtain some relief from lithium, the response rate among those with rapid cycling is only 20-40%. Lithium's effectiveness may be reduced by drug or alcohol dependence; however, this relationship does not seem strong enough to account for the great difference in response rates.
The disappointing results obtained with lithium in the treatment of rapid cycling led researchers to seek alternative treatments. When divalproex sodium (Depakote®) was approved in 1995 by the U.S. food and Drug Administration (FDA) for the treatment of mania associated with bipolar disorder, it brought new hope to patients experiencing rapid cycling and mixed states. Carbamazepine (Tegretol®), although not FDA approved as a treatment for bipolar disorder, sometimes is used as a supplement or alternative to divalproex sodium and lithium.
Divalproex sodium and carbamazepine have been effective in treatment of lithium-resistant rapid cycling and mixed state patients. Their effectiveness appears unconnected to their common identity as anticonvulsants used to treat epilepsy. Not only do the individuals they benefit typically show no sign of epilepsy, but some other drugs that are effective as anticonvulsants provide no help in treating bipolar disorder. Further, whether a patient is helped or not helped by one anticonvulsant does not predict whether that same patient will or will not respond to another. Therefore, people with bipolar disorder should not give up hope if their first course of treatment is not successful.
Reasoning that rapid cycling may be due to inadequate thyroid hormone in the brain, several studies have investigated treating rapid-cycling patients with high doses of the thyroid hormone, thyroxine. Despite their small size, these studies have produced favorable results even in individuals without\ a history of thyroid problems.
As noted earlier, antidepressants may trigger rapid cycling. While stopping antidepressant use may seem logical in these situations, the results can be frustrating. A person with bipolar disorder often experiences depression when not taking antidepressant medication. The availability of treatments other than lithium suggests the more complex strategy of adding thyroid hormone or an anticonvulsant to antidepressant therapy may be a more promising approach. The limited data available from studies of thyroid hormone and anticonvulsants suggest this may indeed be the case.
Alternatives to divalproex sodium, lithium and carbamazepine are understudy in rapid cycling. They include another anticonvulsant, lamotrigine (Lamictal®), and an antipsychotic medication, olanzapine (Zyprexa®). These medications are not approved by the FDA for treatment of bipolar disorder, but patients with rapid-cycling illness may want to discuss them with their doctors.
Psychotherapy is an important supplementary treatment to medication. Along with continuous vulnerability to future episodes, people with any type of bipolar disorder experience complications as a result of past episodes. For instance, people who cry easily may be dismissed as weak. People who are always "in a bad mood" may appear less attractive. Because people with bipolar disorder are often unfairly judged, they may lose opportunities to develop friendships or romantic involvements, or have trouble achieving their career goals. The struggles people with bipolar disorder face may contribute to self-esteem problems. That's why patients may want to consult their mental health professionals about one-on-one psychotherapy with interpersonal, cognitive or behavioral approaches or the benefits of couples, family, and group therapy.
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The 60% Rule for Bipolar Disorder
While there are lots of lectures on bipolar disorder, the facts and figures
become hard to discern. In order to identify some important aspects of bipolar
disorder and its treatment, we need a figure that applies to treatment,
comorbidity and adherence.
1. The 60% rule - A way to identify several features using one figure (60%).
2. Treatment Response: While it is difficult to tell which patients with
Bipolar Disorder will respond to Pharmacological Treatment for Acute Mania, on
average a patient entering treatment for mania will respond about 60% of the time
3. This means that about a 60% response rate for a novel AP (antipsychotic),
60% for MS (a mood stabilizer).
4. This means that if treatment were combined the response rate might be 84%
{AP (60%) + MS (60% of 40 NR) = 84% }
5. Adherence - AP + MS - 1 = 1. In the course of bipolar disorder,
discontinuation of at least 1 medication is to be anticipated. This failure to adhere
to treatment is probably a result of the illness with exacerbation and
remissions and some lack of insight (or reasonable doubt) about the need to continue
meds in maintenance phase.
6. How many patients with Bipolar disorder stop one medication in one year?
(60%)
7. How many patients with bipoalr disorder on combined therapy stop both
medications? Probably less than those on monotherapy (16%?).
8. Comorbidity of Bipolar Disorder - 60% may have psychosis because about 60%
have had psychosis in their lifetime co-morbid Axis I disorders.
9. Comorbidity of Bipolar Disorder - 60% have co-morbid Axis I disorders,
about 60% of those with Axis I comorbidity have an Anxiety disorder
10. Comorbidity of Bipolar Disorder - 60% may have alcohol or substance abuse
because about 60% have had alcohol or substance abuse in their lifetime.
11. Certainly at the time of admission up to 60% of patients with Acute mania
may have active alcohol or substance abuse in an effort to self-treat or
respond to mania itself. Of course, alcohol and drugs of abuse are incendiary to
mania.
12. 60% of bipolar patients will have marital or relationship problems that
may benefit from some form of counseling.
A-typical anti-psychotics with indications for bipolar disorder. (Seroquel, Risperidol, Zyprexa, Abilify)
Seroquel:
Public release date: 12-Jun-2003
Shire Health International
http://www.psychiatry-in-practice.com
Potential new treatment for people with manic depression
Alderley Park, UK – AstraZeneca has announced that it has submitted an application to the U.S. Food and Drug Administration (FDA) for quetiapine (Seroquel) to be granted a licence for the treatment of acute mania associated with bipolar disorder (manic-depressive illness).
The application to the FDA follows the completion of a comprehensive clinical trial programme in bipolar disorder undertaken by AstraZeneca. The trials examined the efficacy and tolerability of quetiapine in the treatment of acute mania on two levels: as monotherapy (i.e to be prescribed on its own) and as adjunctive therapy with standard mood stabilising medication. These clinical trials have delivered strong and positive results in both the monotherapy and adjunctive therapy studies, which confirm quetiapine to be an ideal first line therapy for the treatment of acute mania associated with bipolar disorder.
"Quetiapine is destined to be an important treatment option for patients suffering from bipolar disorder" commented Dr. Gary Sachs from Harvard Medical School, Boston, and lead investigator on the studies. "Treatment compliance in bipolar disorder is particularly critical since patients may lead full and productive lives when stable while a relapse in symptoms can cause real difficulties. The ability of quetiapine to improve the symptoms of the disease while keeping side effects to a minimum, may improve quality of life and ultimately lead to greater compliance with medication, offering real benefits for patients and their families."
The trial programme consisted of four studies involving almost 1000 patients in 28 countries. The results from one of the adjunctive therapy studies were presented earlier this year at the 3rd European Stanley Foundation Conference in Bipolar Disorder, in Germany1. The results from this trial showed that quetiapine, in combination with standard mood stabilising medication (lithium or divalproex), is significantly more effective at treating the acute mania associated with bipolar disorder than mood stabilisers alone. Importantly, the results also showed that quetiapine in combination with mood stabilisers is well tolerated – a major consideration in the treatment of this disorder. The results from the remaining monotherapy studies will be presented at major psychiatry conferences in 2003.
"We are very pleased with the results of the trial programme and are extremely optimistic about the future for Seroquel. Seroquel is a truly unique compound and its profile is ideal for the treatment of bipolar disorder" commented Geoff Birkett, Global Vice President, CNS, Pain and Infection. "Success in the market is driven by the impact on patients and our vision to introduce therapies that truly change patients' lives for the better. With its expanded indication range, Seroquel will continue to help patients and is the cornerstone of our rapidly growing CNS business."
Seroquel (quetiapine) is manufactured by AstraZeneca and is currently approved in over 75 markets. Seroquel combines broad-based efficacy in the treatment of positive, negative, cognitive and affective symptoms of schizophrenia, while offering excellent tolerability. Seroquel is associated with an incidence of EPS and prolactin elevation no different to placebo across the full dosage range, a favourable weight profile, and no clinically important effects on QT interval. To date, over 4 million people have been treated with Seroquel worldwide.
tronic and downloadable version of this press release or for further information about Seroquel, please visit the psychiatry resource internet site at: http://www.psychiatry-in-practice.com
This psychiatry resource features educational materials relating to severe mental illness, including background information on schizophrenia as well as epidemiological data and treatment issues clinicians face in everyday practice.
References:
1. Brecher M & Huizar, K Quetiapine Monotherapy for Acute Mania Associated With Bipolar Disorder. Poster presented at 5th International Congress on Bipolar Disorder, Pittsburgh, 2003
2. Paulsson B & Huizar, K. Quetiapine Monotherapy for the Treatment of Bipolar Mania. Poster presented at 5th International Congress on Bipolar Disorder, Pittsburgh, 2003 3. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000:385, 395.
4. Hirschfield et al. J Clin Psychiatry. 2003;64:53-59
5.Lisd JD, Dime-Meenan S, Whybrow PC et al. The National Depressive and Manic-Depressive Association (DMDA) survey of bipolar members. J Affect Disord. 1994;31:281-294.
6. World Health Organization and the World Bank. The Global Burden of Disease: Summary. Cambridge, Mass: The Harvard School of Public Health Harvard University Press, 1996.
7. Miklowitz D. The Bipolar Disorder Survival Guide. New York: The Guilford Press, 2002.
8. Sachs G, Mullen JA, Devine NA. Quetiapine vs placebo as adjunct to mood stabilizer for the treatment of acute mania. Bipolar Disorders. 2002;4(issue S1);Abs 61:133.
Resperidol, has also demonstrated efficacy in the treatment of manic episodes in bipolar disorder, both as monotherapy and as an adjunct to mood stabilizers.
Risperdal® (risperidone) produces continuous improvement of 'manic' symptoms in bipolar disorder
Risperdal monotherapy better tolerated than 'gold standard'
21 September 2003 – Prague – When used alone, RISPERDAL® (risperidone) significantly improves symptoms of acute mania in persons with bipolar disorder as early as one week after treatment begins, according to data presented today for the first time at the 16th Congress of the European College of Neuropsychopharmacology (ECNP)1. Treatment with Risperdal also was associated with a lower incidence of extrapyramidal symptoms (movement disorders) than the older conventional antipsychotic haloperidol, which should make it easier for more patients to take their medication consistently.
Bipolar disorder is a serious psychiatric illness affecting approximately three percent of the worldwide population. People with bipolar disorder experience dramatic mood swings, from deep depression to acute mania (characterised by symptoms such as excessively "high" mood, racing thoughts, poor concentration and unrealistic beliefs about their own abilities and powers).
The double-blind study presented at the meeting was conducted over the course of 12 weeks. In the initial three-week period, 438 patients with bipolar mania were randomly assigned to take risperidone, haloperidol or placebo. After the three weeks, patients still on active therapy could continue on 'blinded' treatment (risperidone or haloperidol, without knowing which medication they were receiving) for a further nine weeks, while those receiving placebo were switched to risperidone. During the total 12-week study period, the mean modal doses were 4.1 mg/day for risperidone and 7.4 mg/day for haloperidol.
During the initial three-weeks, efficacy was measured using the Young Mania Rating Scale (YMRS). Significantly greater improvements were seen in those who took risperidone or haloperidol than in those who received placebo.
By the end of this period, treatment response was achieved by 48 percent of risperidone patients and 47 percent of the haloperidol group, compared with just 33 percent of people who received placebo.
Treatment response was defined as a reduction in the total YMRS score that was greater than or equal to 50 percent. Response was significant at the first, second and third weeks for treatment with risperidone, whereas for haloperidol, the difference from placebo was significant only at week two. During the 12-weeks of double-blind treatment further improvements were seen. While 50 percent of the original risperidone group completed 12 weeks of double-blind treatment, only 39 percent of the haloperidol group did so, with side effects the main reason for discontinuation.
One of the potential risks associated with treating bipolar patients with manic symptoms is the possibility of triggering depression. In this study, Risperdal treatment improved symptoms of depression in patients with bipolar disorder. In contrast, haloperidol improved depressive symptoms at some points in time, it did not do so at others. The research also showed that Risperdal was better tolerated than haloperidol, with a lower incidence of extrapyramidal symptoms (EPS). EPS frequently result from treatment with antipsychotic medication and include movement disorders or muscle disturbances such as restlessness, muscular spasms, tremors and muscle stiffness.
"These data, together with other study findings, indicate that risperidone can significantly and rapidly alleviate acute mania when given alone or in combination with mood stabilisers," said Professor Allan Young, honorary consultant with the Department of Psychiatry, University of Newcastle in the UK. "Perhaps the most important finding from this study is that regardless of the presence or absence of psychosis, risperidone was consistently effective in reducing the symptoms of mania."
Risperdal is the world's most widely prescribed, newer-generation ('atypical') antipsychotic. It is approved for a variety of conditions in more than 80 countries, including treatment of schizophrenia, behavioural and psychological disturbances in patients with dementia, acute mania associated with bipolar disorder and disruptive behaviour disorders.
The formulation of Risperdal can be selected to suit the unique needs of patients; it is available in tablet form (both standard and fast-dissolving), as an oral solution and as a long-acting injection called Risperdalâ Constaä, the first long-acting formulation of a modern antipsychotic. It is administered just once every two weeks, rather than daily.
###
For further information, contact:
Pam Rasmussen
Johnson & Johnson
Global Pharmaceutical Communications
Worldwide
+1 609-730-2986 (U.S.)
prasmus@gpcus.jnj.com
Brigitte Byl
Johnson & Johnson
Global Pharmaceutical Communications
Europe, Middle-East, Africa
+32 (0)2-749-2772 (Belgium)
bbyl@gpcbe.jnj.com
Notes to editor:
The Janssen-Cilag companies, which are members of the Johnson & Johnson (NYSE:JNJ) family of companies, one of the world's most diversified healthcare corporations - have a long track record in developing and marketing treatments for central nervous system disorders, pain management, fungal infections and gastrointestinal conditions. Leading products include Concertaâ (ADHD), Durogesicâ (pain management), Eprexâ (anemia), Parietâ (gastroenterology), Topamaxâ (epilepsy), Reminylâ (Alzheimer's disease) and Risperdalâ (schizophrenia). More information can be found at www.psychiatry24x7.com or at www.janssen-cilag.com
References:
1. Kramer M, Karcher K, Grossman F. Risperidone monotherapy in acute bipolar mania. Presented at the 16th ECNP in Prague, 20-24 Sept 2003
OLANZAPINE, FDA Approval for Bipolar
FDA Approves Zyprexa (Olanzapine) For Manic Episodes In Bipolar Disorder
INDIANAPOLIS, IN -- March 20, 2000 -- Eli Lilly and Company announced that the U.S. Food and Drug Administration (FDA) has approved Zyprexa(R) (olanzapine) for marketing for the short-term treatment of acute manic episodes associated with bipolar disorder.
Bipolar disorder, also known as manic depressive illness, is a lifelong illness characterized by disruptive swings in mood -- from manic episodes, marked by euphoria and irritability, to periods of depression. Mania is a period of abnormal elation and/or irritability, often accompanied by an unrealistic belief in one's own abilities, increased sex drive, delusions, and alcohol or drug abuse. People with bipolar disorder also may experience mixed episodes, marked by symptoms of mania and clinical depression occurring simultaneously.(1)
Approximately three million Americans suffer from bipolar disorder.(2) An estimated one in four persons with the illness attempts suicide, one of the highest incidence-rates for any psychiatric disorder.(3)
"In short-term clinical trials, it appears that Zyprexa acts as a mood stabilizer to manage the manic phase of bipolar illness easily, safely and effectively. Additionally, unlike some other medications, Zyprexa does not require blood monitoring," said Mauricio Tohen, M.D., Dr. P.H., lead investigator, Lilly Research Laboratories. "Zyprexa can stabilize mood in a range of bipolar patients with manic symptoms, potentially avoiding impulsive or reckless behavior that can lead to serious problems."
Mania associated with bipolar disorder, while manageable with proper therapy, can be difficult to diagnose and, therefore, may be treated incorrectly.
"The majority of patients with bipolar disorder seek treatment during a depressive phase. This can leave the manic phase of the disease undetected, leading to inappropriate treatment and worsening of symptoms," said Paul Keck, M.D., professor and vice chairman for research, University of Cincinnati College of Medicine. "Accurate diagnosis and proper treatment are critical to managing the illness and allowing people the chance to lead healthy, productive lives."
The FDA's approval of Zyprexa for the treatment of acute manic episodes associated with bipolar disorder was based on results from two placebo-controlled trials involving patients with a primary diagnosis of bipolar disorder: one three-week trial involving 67 patients and one four-week trial involving 115 patients. The trials included patients with manic and mixed episodes, with or without psychotic features, and with or without a rapid-cycling course.
Zyprexa led to a significant improvement in mania, as measured by the Young-Mania Rating Scale (YMRS).
Zyprexa was generally well tolerated, with four adverse events reported significantly more frequently in the Zyprexa group than in the placebo group: somnolence (drowsiness), dry mouth, dizziness and asthenia (loss of strength). No participants discontinued the study due to any of these events. Other common events that did not separate statistically from placebo were constipation, dyspepsia (indigestion), increased appetite, and tremor.
The recommended beginning dose of Zyprexa to treat acute manic episodes is 15 or 10 milligrams, taken once a day, at any time, without regard to meals.
Zyprexa also is indicated in the United States for the management of the manifestations of psychotic disorders as demonstrated in short-term clinical trials with schizophrenia patients. Since Zyprexa was introduced in 1996, it has been prescribed to nearly four million people worldwide.
In the original schizophrenia registration trials, Zyprexa was generally well tolerated. However, as with all medications, Zyprexa was associated with some side effects. In the original six-week, acute-phase schizophrenia trials, the most common treatment-emergent adverse event associated with Zyprexa was somnolence. Other common events were dizziness, weight gain, constipation, akathisia (restlessness) and postural hypotension. Modest elevations of prolactin were also seen, although mean changes from baseline to
endpoint were not statistically significantly different between Zyprexa and placebo. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients developed jaundice or drug-induced hepatitis.
Eli Lilly and Company is a global research-based pharmaceutical corporation headquartered in Indianapolis, Ind., that is dedicated to creating and delivering innovative pharmaceutical-based health care solutions that enable people to live longer, healthier and more active lives.
Zyprexa(R) (olanzapine, Lilly)
References
(1) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). American Psychiatric Association, 1994.
(2) Practice Guideline for Treatment of Patients with Bipolar Disorder. American Psychiatric Association, 1995.
(3) Goodwin FK, Jameson, KR. Manic Depressive Illness. Oxford University Press, 1990.
Related Links: Zyprexa (olanzapine) and Eli Lilly and Company.
Abilify, A-typical with indications for Bipolar:
Results From New Clinical Studies: Aripiprazole Significantly Improved Symptoms of Acute Bipolar Mania
Results Presented At 2003 American Psychiatric Association Annual Meeting
May 20, 2003
Patients with bipolar disorder experiencing an acute manic episode who received treatment with aripiprazole (Abilify) showed significant improvement in their symptoms and significantly higher response rates compared to either haloperidol (Haldol) or placebo, according to two studies presented today at the 156th Annual Meeting of the American Psychiatric Association. In addition, the discontinuation rate due to adverse events for aripiprazole was significantly lower than that for haloperidol and similar to that for placebo.
"In these studies, Abilify improved symptoms of bipolar mania, with rapid onset of effect as early as Day 4," said Paul Keck, M.D., Professor of Psychiatry, Pharmacology and Neuroscience, and Vice Chairman for Research, Department of Psychiatry, University of Cincinnati College of Medicine. "These data are consistent with the results of a previous study in which aripiprazole was effective in treating acute mania in patients with bipolar disorder."
In a 3-week, double-blind, placebo-controlled trial of 272 in-patients with bipolar disorder experiencing an acute manic episode, patients were randomized to receive either placebo or a starting dose of 30 mg/day of aripiprazole, with the option to decrease dosage to 15 mg/day (mean dose: 27.6 mg/day). Aripiprazole produced significantly greater improvements in Young Mania Rating Scale (Y-MRS) score by Day 4 compared to placebo (-8.17 vs. -5.37; p<0.002); this separation increased throughout the 3-week treatment period (Week 3: -12.52 aripiprazole vs. -7.19 placebo; p<0.001). In addition, significantly more patients responded to treatment with aripiprazole compared to placebo (53% vs. 32%; p<0.001) at Week 3. Response was defined as a 50% or greater improvement from baseline Y-MRS score.
Aripiprazole produced significant improvements versus placebo in Clinical Global Impression-Bipolar Disorder (CGI-BP, p=0.009 at Week 3), Positive and Negative Syndrome Scale (PANSS)-Total (p=0.011) and PANSS hostility subscale (p=0.002) scores. In terms of weight change, similar percentages of patients receiving aripiprazole and placebo experienced clinically significant weight gain (defined as ³7% weight gain). There was no significant difference in the rate of extrapyramidal syndrome (EPS) between aripiprazole and placebo. Discontinuations due to adverse events were similar between aripiprazole and placebo. In this study, the most commonly reported adverse events for aripiprazole (greater than 5% and two-times placebo) were akathisia, dyspepsia and constipation.
In a separate 12-week, multicenter, double-blind study of 347 in- and out-patients with acute mania, a significantly greater percentage of patients responded to treatment with aripiprazole compared to patients treated with haloperidol at Week 12 (49.7% vs. 28.4%; p<0.001). Response rate was determined by the percentage of patients who exhibited a 50% or greater improvement from baseline on the Y-MRS score and who were still on treatment at Week 12. Patients in this study were randomized to receive either 15 mg/day of aripiprazole or 10 mg/day of haloperidol, with the option to increase doses to a maximum of 30 mg/day of aripiprazole or 15 mg/day of haloperidol.
While both drugs produced similar improvement in mean Y-MRS and Clinical Global Impression (CGI) Severity scores, significantly more patients treated with aripiprazole remained in the trial compared to those treated with haloperidol (50.9 vs. 29.1%; p<0.001). Discontinuations due to adverse events were 49.1% in the haloperidol group compared to 18.9% in the aripiprazole group. Patients treated with haloperidol also experienced a significant increase in extrapyramidal symptoms (EPS) compared to aripiprazole patients, as measured by mean change from baseline to endpoint in the Simpson-Angus Scale (1.02 vs. 5.70, respectively; p<0.001), the Barnes Akathisia Scale (0.32 vs. 0.80 respectively; p<0.001) and the Abnormal Involuntary Movement Scale (0.14 vs. 0.81 respectively; p<0.002). In addition, patients treated with haloperidol experienced a significant increase in prolactin levels compared to a decrease for patients taking aripiprazole (p<0.001). Weight change associated with aripiprazole and haloperidol was +0.27 kg and- 0.10 kg, respectively, and no patients in either treatment group experienced clinically significant increases in QTc interval. The most commonly observed side effects associated with aripiprazole in this study (incidence rate of greater than 10%) were insomnia, depression, akathisia, and headache; the most common side effects with haloperidol were EPS, akathisia, depression, headache, and tremor.
About Aripiprazole
Aripiprazole, the most recently approved treatment for schizophrenia in the United States, Mexico, Brazil, Puerto Rico, and Australia, has been prescribed for more than 100,000 people in the United States. Aripiprazole is available in 10 mg, 15 mg, 20 mg, and 30 mg tablets. When starting treatment, some patients experience side effects such as headache, anxiety, insomnia, nausea, vomiting, sleepiness, lightheadedness, restlessness, and constipation.
In short-term (4- and 6-week) placebo-controlled trials, there was no statistical difference in the incidence of discontinuation due to adverse events between patients treated with aripiprazole and placebo (7% and 9%, respectively) or incidence of extrapyramidal syndrome (6% vs. 6%). In addition, studies showed that aripiprazole was associated with a moderate difference in sedation compared to placebo (11% vs. 8%, respectively), and did not cause significant QTc interval changes.
Aripiprazole is available by prescription only. Patients should talk to their physician for more information. More detailed prescribing information on Abilify is available here.
Source: News Release from Bristol-Myers Squibb
If you participated in the Abilify Bipolar clinical trials, are taking this medication, or have comments on this new drug, how about sharing them on our bulletin board.
More on Abilify:
Abilify Pharmacology - Usage, Dosage, Side-Effects
Abilify Approved For Maintainence Therapy - Low Weight Gain, No Link to Diabetes
Psychiatrists Expect to Increase Usage of Abilify
Aripiprazole (Abilify) Not Associated with Increased Diabetes Risk
Abilify (Aripiprazole) Demonstrates Better Weight Change Profile Than Olanzapine (Zyprexa)
Abilify (Aripiprazole) Improves Symptoms in Patients With First-Episode Schizophrenia
Abilify For Long-Term Schizophrenia Treatment
Abilify: A Breakthrough For Schizophrenia Patients
"Abilify" (Aripiprazole) Gets FDA Approval
Bristol's Schizophrenia Drug, Abilify, Gets Conditional OK
"Abilify" (Aripiprazole) Antipsychotic Drug; Pre Approval Data
Bristol-Myers's Antipsychotic Produces Fewer Side Effects
Bristol-Myers: Aripiprazole Effective vs Schizophrenia
http://www.Healthyplace.com
Mania is derived from the Greek word meaning, "a state of raving madness". Hippocrates is credited with introducing mania (and melancholia) into medical nomenclature. From that time until modern classification, the diagnosis of mania seemed to have been used primarily for an illness with an acute onset and with a mood of merriment or rage or fury. It must be said that the recognition of mania and the occurrence of mania were apparent to clinicians throughout history.1 Mania in its varied forms (mixed, dysphoric, catatonic, psychotic and due to a general medical condition) requires careful recognition and treatment.
Brendan T. Carroll, M.D.
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DEFINITIONS OF LOADING
The "loading dose" is one or a series of doses that may be given at the onset of therapy with the aim of achieving the target plasma concentration rapidly.3 Multiplying the target steady state plasma concentration (CSS ) by the Volume of Distribution (VD) gives the calculated loading dose (i.e. LD = CSS x VD).
A loading does may be desirable if the time required to attain steady state by a consistent rate (four elimination half-lives) is long relative to the temporal demands of the condition being treated. The use of a standard loading dose also has significant disadvantages. The particularly sensitive individual may be exposed abruptly to a toxic concentration of the drug. Moreover, if the drug involved has a long half-life it will take a long time for the concentration to fall if the level achieved was excessive. Loading doses tend to be large.3
A useful definition for loading is the administration of larger than usual doses of the medication to achieve the desired steady-state blood level (endpoint). Effective medications for the treatment of mania include lithium, valproic acid (i.e. divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, haloperidol and quetiapine.2 Loading strategies for each will be discussed.
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LITHIUM
Lithium has been shown to be an effective antimanic agent.4 It is generally tolerated by patients with acute mania. Unfortunately, it may take 4-10 days for the patient to respond after achieving a serum lithium concentration of 0.9-1.4 mEq/L. Accuracy is necessary in dosing since there is a fine line between high therapeutic level (<1.4) and clinically toxic levels (>1.5 mEq/L). A loading strategy for lithium should target the therapeutic range without crossing the line of toxic threshold. There are two loading strategies that also give a reasonable estimate of the doses needed for the desired steady-state endpoint (e.g. 0.8-1.0 mEq/L).
This is a Single-Point Method.5 This uses a test or loading dose of 1200 mg of LiCO3. The patient’s blood is drawn 24 hours after this dose. The serum lithium level is compared on the lithium nomogram against the desired level and the lithium maintenance dose is found at the intersection of these two points. A similar method, using a 600 mg lithium dose, was used successfully to predict lithium dosage in 16 conduct-disordered children (ages 8 to 17 years).6 A lithium nomogram is shown above.
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DIVALPROEX
Many studies have suggested that valproic acid in the form of divalproex sodium can be loaded orally in patients with acute mania.12,13,14 Oral loading of valproic acid has only been reported with the commercial preparation of divalproex sodium (Depakote - Abbott Labs) tablets. Valproic acid preparations (Depakene - Abbott Labs, liquid concentrates and generic preparations of valproic acid) have not been tested using this method and based on their composition they are not likely to be well tolerated.11
We used the method proposed by Keck et al and found it to be generally well tolerated.12 In this method there was no increase in the side effects of divalproex. Once the patient was determined to be a candidate, oral divalproex loading began that day. The conversion factor is 20 mg/kg/day. Alternatively, this involves adding a zero to the weight in pounds. This amount is given in single or divided doses the first day and then continued for 4-7 days. Blood levels were drawn on the 4th day. Clinical improvement may be seen in the first week. Some have reported that divalproex could be loaded in those patients on lithium or antipsychotics without significant adverse effects. Oral divalproex loading appears to be a useful treatment strategy for the treatment of acute mania and mixed states. Furthermore, Keck found that this strategy reduced inpatient psychiatric length of stay.13
Recently, a more aggressive loading strategy has been promoted: 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg on days 3 to 10.14 Accelerated oral loading with divalproex sodium achieved valproate levels above 50 mcg/mL in 84% of patients by day 3. There was some suggestion of increased efficacy with rapid loading. There were no reported increases in adverse effects.
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When loading divalproex in patients on other medications one should remember that it tends to inhibit the metabolism of other medications. Side effects such as sedation, alopecia, abdominal pain, diarrhea, weight gain, tremor and others may require observation and possibly further treatment. Pancreatitis, hepatitis and allergic reactions are rare and may require discontinuation. Divalproex loading is not recommended for patients with hepatic dysfunction, with known hypersensitivity to valproic acid, the elderly and women who are pregnant or actively breastfeeding.
The intravenous loading of valproate (Depacon) has been used in Germany for the treatment of acute mania. While this is not an FDA (U.S. Food and Drug Administration) approved indication for the intravenous preparation of valproic acid, it may present a treatment option for patients who fail oral loading strategies.15 Initial daily doses were either 1200 mg per day or 1800 mg per day based on the patient’s weight. Valproate sodium injection was given in 600 mg, 60-minute infusions.15
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