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Bipolar Disorder

UNDERSTAND AND PREVENT BIPOLAR DISORDER

 

This course is about a mood disorder that is so commonly discussed in the media of late-bipolar disorder. Although this disorder is not as common as depression, the number of bipolar disorder diagnoses appears to be rising, mainly because of new research and consideration of symptoms that do not meet the full criteria for bipolar but do have many similar symptoms that cause significant impairment. Such symptomatology may comprise other bipolar categories that are considered part of the “bipolar disorder spectrum.” 

(41) Bipolar Disorder

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BD41

My internist is prescribing an antidepressant. How do I know if I should see a specialist? Should I see a psychiatrist?

A general practitioner of medicine can often adequately treat depression. There are situations, however, when a psychiatric consultation should be obtained. If co morbid conditions such as anxiety or substance abuse, severe suicidal thinking, or complicated personality issues exist, a psychiatrist is better equipped to manage the antidepressant treatment. In particular, the psychiatrist may be able to provide more frequent contacts and have longer sessions than the general practitioner typically has available. Two problems that arise when depression is treated by a general practitioner is the potential for under-dosing of medication as well as a too-short duration of treatment. Certainly if the depression is not responding to a prescribed treatment, consultation with a specialist is warranted as well. In the case of bipolar depression, however, or if there is concern because of a family history of bipolar disorder, it is usually best that a psychiatrist prescribe and monitor the symptoms, as management of the depression is typically more complicated.  Some individuals seek the services of a psycho pharmacologist.

The term can be somewhat misleading, as it implies a specialty in medication management of psychiatric conditions. In fact, all general psychiatrists are adequately trained in pharmacotherapy of mental disorders and need not be designated as psycho pharmacologists.

Some psychiatrists restrict their practice to medication management of mental disorders and thus are self-described as psycho pharmacologists. There are psychiatrists who develop more expertise in the management of certain conditions and use of some medications, by virtue of clinical experience and perhaps research in academic settings, and thus may take referrals from other psychiatrists (and mental health clinicians) for more refractory conditions. In general, however, seeking consultation from a general psychiatrist is usually appropriate for most emotional problems. Specialists may be sought within the field of psychiatry for treatment of children and adolescents (child and adolescent psychiatrist), elderly (geriatric psychiatrist), medically ill (consultation-liaison psychiatrist), and individuals with substance abuse (addiction psychiatrists).

Why do I need a mood stabilizer with my antidepressant if I am depressed but not manic?

The term mood stabilizer has a variety of meanings attached to it. For the lay public, any medication that helps even out one’s moods, including an antidepressant medication, is a mood stabilizer. For most psychiatrists the term mood stabilizer includes a class of medications that treat and prevent mania.

These medications typically include anticonvulsant medications such as Depakote (valproic acid) and Equetro (carbamazepine); atypical antipsychotic medications such as Zyprexa (olanzapine), Seroquel (quetiapine), and Risperdal (risperidone); andlithium. The definition of a true mood stabilizer, however, is a medication that treats and prevents both depression and mania. There is no true mood stabilizer by that definition. Perhaps lithium comes the closest to meeting that definition, though it does not truly compare to antidepressants in effectively treating depression. Other antimanic medications that are never thought of as mood stabilizers include the anti-anxiety medications. At one time, alprazolam was used to treat certain forms of depression as well as anxiety and mania.

Thus, when a psychiatrist adds a “mood stabilizer” to an antidepressant you need to know exactly what class of agent is being prescribed and for what purpose. Many patients may have associated symptoms with their depression such as psychosis, and therefore an atypical antipsychotic medication is an appropriate addition to the antidepressant. Still other patients may experience a great deal of anxiety and panic, in which case the addition of an anti-anxiety agent may be appropriate. Some patients may never have had a manic episode, but some of their symptoms and family history are strongly suggestive of an underlying bipolar disorder. Under these circumstances, the safest medication to prescribe may be a mood stabilizer alone, unless the depression is severe enough to warrant aggressive care, in which case the psychiatrist may add an anticonvulsant, lithium, or an atypical antipsychotic as a preventative measure. Finally, some patients may only achieve a partial response to the antidepressant.

When a partial response is achieved, the psychiatrist will typically add another medication to augment the primary medication’s response rather than switch the medication altogether.

Leslie’s comments:

I went to my primary care physician when I finally decided to get help with my illness. I was, unfortunately, misdiagnosed and as a result was treated only for depression. My physician prescribed an antidepressant, which caused me to become hypomanic and then plummet to the point of causing me to get into a car accident. My physician told me to stop taking the medication but I had terrible side effects as a result of that process. I then began seeing a psychiatrist, someone who specialized in the diagnosis and treatment of mental disorders. It was at that time that I was properly diagnosed with bipolar disorder and began my treatment with the medications that ultimately got my symptoms in check. That all happened about nine years ago and I now see a Clinical Nurse Specialist who is responsible for prescribing and monitoring my medication.

I have been prescribed a medication “off-label.” Does that mean it is experimental?

The term off-label is used when a medication is used in a manner that is not FDA approved. Does this mean the medication is experimental? No, absolutely not. This means simply that no studies have been submitted to the FDA for approval of the medication for that particular use. It does not mean that no studies have been done. There are many studies that may not have been submitted, or that have been submitted and approved by European governments. It does not mean that the medication is not widely prescribed for a use other than what the FDA approved.

It does not mean that doses under or over the recommended range approved by the FDA are neither effective nor safe. It does not mean that the medication is not safe in age groups younger or older than what the FDA approved. It merely means that when the company submitted the medication for approval to the FDA it submitted studies that specified a diagnosis, a dosage range, and an age group that their study subjects reflected.

Drug research and development have a fascinating history.

Psychiatric drugs are often discovered serendipitously. Most drugs have multiple effects on the body, and focusing on one particular action to the exclusion of another is often as much a matter of marketing as it is drug action. For example, the first antipsychotic medication was developed and tested by a trauma surgeon who was specifically interested in finding a medication that could prevent surgical shock, a condition with a high mortality rate at the time. It was only through clinical observation that the medication was discovered to have antipsychotic effects as well as a variety of other effects on the body. The company that originally introduced it to the United States did not believe there would be a market for it as an antipsychotic and so released it to the public as an antiemetic.

Only through multiple physician-driven lectures were psychiatrists in the United States comfortable enough to try it on patients suffering from schizophrenia. Perhaps even odder is the fact that the first antidepressant effects were observed in medications developed to treat tuberculosis. Only later was it discovered that these medications inhibited, or blocked, monoamine oxidase, an enzyme that breaks down norepinephrine, serotonin, and dopamine at the synaptic cleft.

To call any particular medication an antihypertensive, an antipsychotic, an antidepressant, or an anticonvulsant is actually a misnomer and really reflects the target population that a particular medication is geared toward when released to the public, not the broad range of effects of which the medication is capable. It also reflects the expense the companies go through in order to obtain FDA approval.

The FDA requires that each medication target a specific diagnosis in order to receive approval, which is a hugely expensive enterprise for one diagnosis, much less for multiple diagnoses. Therefore, it is unlikely that drug companies will submit studies for approval for more than one or two diagnoses unless they can see some return on investment. As a result, clinical practice is often very different from what the PDR publishes.

Clinical practice moves at a much faster pace than clinical trials and publications can keep up with. And while clinical trials are considered to be the definitive evidence of any particular medication’s efficacy, astute clinical observations are what brought the biggest drug discoveries to the world and cannot be discounted simply because no study has yet to be published.

There are two broad reasons why off-label use makes sense in psychiatry. First, psychiatric diagnoses do not fit into the neat little categories the DSM-IV-TR attempts to define. They generally have many overlapping symptoms. For example, anhedonia, or loss of interest, can be seen in a number of conditions that include depression, schizophrenia, and frontal lobe damage. Many psychiatrists believe that medications should be prescribed to target the particular neurochemicals underlying such specific symptoms regardless of the DSM diagnosis. Off-label use is practiced with a clear rationale for another reason as well.

Human nature defies categories. There may be broad similarities between two individuals suffering from depression, but it is doubtful that any one individual is suffering in exactly the same way as another from both a biochemical and psychological standpoint. Thus, one may respond to one particular therapy or antidepressant and not another and the reasons are due to the therapies’ and antidepressants’ biochemical differences, not their similarities. For these reasons, off-label use in psychiatry is more the rule than the exception. Consider this example: a man sought out a cardiologist because he noticed getting palpitations from one particular brand of cola and not another. The cardiologist dismissed him outright.

The man sought out another cardiologist who agreed to perform a stress test after he ingested the different brands, and sure enough, the man experienced premature ventricular beats with one particular brand of cola and not another. Never underestimate the power of one.

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(42) Bipolar Disorder

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BD42

When is hospitalization necessary? What does it offer?

Hospitalization is the highest level of treatment. It is reserved for the most severe forms of mental illness. One criterion used for determining necessity of hospitalization is the presence of suicidality. Having suicidal ideation does not automatically dictate a hospital stay, but it does prompt an inquiry into the patient’s level of risk to harm him or herself (or others).

Hospitalization may also be indicated if a person’s functional impairment is so poor that he or she is unable to adequately care for him- or herself (e.g., unable to get out of bed, not eating), such as in someone with severe depression. Most often, depressed individuals are willing to be hospitalized if recommended and thus do so voluntarily. There are situations, however, when the physician believes hospitalization is necessary but the patient refuses.

This is more likely in cases of mania during which one rarely wants to be hospitalized. The physician then needs to decide if the person should be admitted involuntarily. Criteria for this process vary from state to state, but it is generally not easy to admit someone against his or her will. Most states have mental hygiene laws in place to protect patients’ rights. Typically, dangerousness to self or others is the criterion required to commit someone. In that light, hospitalization for mania is usually due to potential for aggression, psychosis, or severe functional impairment that puts the individual at risk. Mental hygiene laws usually have an appeal process available for those committed involuntarily, and a reassessment is typically required within a specified time period as to necessity for continued hospitalization.

Can I drink wine with my mood stabilizer?

There are two parts to the answer to this question. The first part has to do with alcohol’s effect on the brain of someone with bipolar disorder and the second part has to do with any drug–drug interactions between alcohol and your medication. First of all, alcohol is the last thing you want to put in your body if you suffer from bipolar disorder. Alcohol negatively affects the very chemicals that your mood-stabilizing medication is trying to normalize. Alcohol is a depressant.

Alcohol is a euphoriant. Alcohol can worsen anxiety. Alcohol can worsen irritability. When alcohol is on board it acts as a sedative and can cause some areas of the brain to shut down their control of other more “primitive” areas of the brain, increasing impulsivity and reckless behavior. When alcohol washes out of your system your brain’s activity level increases overall so that your moods end up cycling more rapidly and irritability and dysphoria can increase. Sleep is compromised as well, increasing your chances of relapsing into mania or depression.

In terms of any potential interactions between alcohol and bipolar medications, the answer is more complicated. With some medications like anticonvulsants and benzodiazepines the risk is serious insofar as there is a cumulative sedative effect of the two leading to an increased probability of intoxication and possible respiratory suppression. With other medications, such as the atypical antipsychotics, the risk of having a seizure, while small, is increased. With certain antidepressant medications, such as the monoamine oxidase inhibitors, the risk is serious, as the interaction with some forms of alcohol, particularly red wines, can lead to malignant hypertension, which is potentially life threatening.

With tricyclic antidepressants, the risks are again due to their sedative effects, which are additive to alcohol, and thus cause intoxication and its incumbent risks more readily. Finally, with the newer SSRIs, the additive effects are much less noticeable, as these medications are not found to be sedating nor to affect cognition and motor coordination adversely. Given both the potential for worsening illness, as well as exacerbating symptoms, it is best to avoid alcohol altogether.

Scott’s comments:

The first time I had alcohol while on medication was on my wedding anniversary.My wife and I was staying at a beautiful resort, and decided we’d celebrate with a glass of wine at dinner. That night I had the most incredibly violent dreams that I’ve ever had. My sleep was interrupted with horrible nightmares about bloodshed and killing. The next morning I discussed this with my wife-it was enough to make me swear off alcohol.

Term:

Malignant hypertension - elevated blood pressure that is acute and rapidly progressive with severe symptoms, including headache.

Are there long-term dangers to taking medication?

With the recent press regarding the link between Vioxx and heart disease, and the alleged link between antidepressant medications and suicide, fear of long-term adverse effects has grown, particularly for newer medications. With respect to psychiatric medications, this fear includes the belief that medication is a form of mind control that can have permanent long-term effects on one’s personality and mind. This particular idea is categorically false. No medication has that level of control over one’s mind. With respect to potential long-term adverse effects of various bipolar agents, however, one should be aware of each agent’s particular issues. The most common and/or concerning issue for each is the subject of the following paragraphs. The list is otherwise too long; refer to the package insert for each drug for a complete list.

Lithium

Lithium is the most well known in terms of potential adverse effects. First, it is important to note that blood levels need to be monitored regularly. Lithium has a very narrow therapeutic index-that is, the blood level for minimum effectiveness and the blood level for potential toxicity is fairly narrow. Second, there are three potentially long-term adverse effects of which to be aware and to understand: hypothyroidism, kidney damage, and weight gain. There are a number of risk factors for developing hypothyroidism. They include having a prior history of thyroid problems, being female, being overweight, having a family history of thyroid problems, having rapid-cycling bipolar disorder, and requiring higher doses of lithium. When hypothyroidism develops as a result of lithium it is generally reversible, unless antibodies to thyroid are present. The best indicator for presence of antibodies is family history. If hypothyroidism occurs, thyroid replacement may be indicated. The most common problem that occurs to the kidney in response to lithium is the inability to concentrate urine and preserve fluid over time. The risk of this is both dose and time dependent. That is, kidney toxicity generally occurs after taking higher doses of lithium for many (ten to fifteen) years. Chronic renal failure can occur at this time; lithium needs to be discontinued once this has happened. One should avoid taking nonsteroidal anti-inflammatory medications for extended periods of time as these medications increase the blood level of lithium and can also adversely impact the kidneys.

Weight gain associated with lithium is a slow onset effect. It occurs for a variety of reasons, including the initial increased thirst associated with lithium, the possibility of hypothyroidism from lithium (which can also cause weight gain), and the effect of lithium itself on metabolism. Risk factors associated with weight gain include being young, overweight, and female. The odds of gaining weight are about 50/50.

Terms:

Therapeutic index - the ratio between the toxic dose and the therapeutic dose of a drug, used as a measure of the relative safety of the drug for a particular treatment.

Hypothyroidism - decreased or absence of thyroid hormone, which is secreted by an endocrine gland near the throat and has wide metabolic effects. When thyroid hormone is low, metabolism can slow, leading to symptoms that can mimic clinical depression.

Depakote (valproate)

Depakote (valproate) has some immediate and long-term adverse effects. The immediate concern for various blood disorders prompts monitoring of a complete blood count. Thrombocytopenia, a drop in platelets (important in blood clotting), is a not uncommon effect. This is easily reversible by stopping the medication.

Hepatitis and pancreatitis can also occur early on in treatment, and for this reason liver function tests should be performed regularly.Women of childbearing age should be cautioned, as Depakote (valproate) is associated with a higher incidence of birth defects. A more common, less dangerous, but more distressing problem is alopecia, or hair loss. This is also reversible with discontinuation of the medication.Weight gain is a potential problem, and Depakote (valproate) may play a role in the development of polycystic ovarian syndrome.

Terms:

Thrombocytopenia - an abnormal decrease in the number of platelets in the blood.

Hepatitis - inflammation of the liver, caused by infection or a toxin.

Pancreatitis - inflammation of the pancreas

Equetro (carbamazepine)

Although reported infrequently, serious adverse organ system effects have been observed with the use of Equetro (carbamazepine). Early in treatment a rash is possible. Most rashes are benign. Should signs and symptoms of a severe skin reaction such as Stevens-Johnson syndrome appear, Equetro (carbamazepine) should be withdrawn immediately. Blood cell problems are the most well known complications. Both leucopenia (loss of white blood cells) and thrombocytopenia can occur. In addition, the liver can be adversely affected, resulting in hepatitis and jaundice. Equetro (carbamazepine) levels, a complete blood count, and liver function must be monitored throughout treatment in order to detect as early as possible signs and symptoms of a possible blood or liver problem. Equetro (carbamazepine) should be discontinued if any evidence of a significant problem appears. Long-term toxicity studies in rats have indicated a potential carcinogenic risk; however, no evidence exists that this medication is carcinogenic in humans. In women of childbearing potential, Equetro (carbamazepine) should be avoided whenever possible or prescribed as monotherapy because the incidence of congenital abnormalities in the offspring of women treated with more than one anticonvulsant is greater.

Terms:

Stevens-Johnson syndrome - a severe inflammatory eruption of the skin and mucous membranes that can occur as an allergic reaction to a medication.

Leucopenia - an abnormal lowering of the white blood cell count.

Atypical Antipsychotic Medications

Although the FDA treats the atypical antipsychotics as a class in terms of side effect profiles, all coming with the same warnings on their package inserts, they do not all demonstrate the same adverse effects equally. The most concerning class effect is the development of metabolic syndrome, which is characterized by a number of metabolic changes, including weight gain and elevated cholesterol, triglycerides, and fasting blood sugars. Some patients have gone on to develop diabetes.

A few have developed diabetic ketoacidosis, a medical emergency stemming from extremely high blood sugars. Not all of the atypical antipsychotics appear to cause this problem to the same degree. The two worst offenders are Clozaril (clozapine) and Zyprexa (olanzapine). This is unfortunate, because Clozaril (clozapine) is the most effective antipsychotic on the market, and many clinicians swear by Zyprexa (olanzapine) as being the second most effective and perhaps best-tolerated agent. In the middle are Risperdal (risperidone) and Seroquel (quetiapine).

Geodon (ziprasidone) and Abilify (aripiprazole) appear to have no effect on the development of metabolic syndrome though both have been known to cause weight gain to a lesser degree than the others. All of these medications have been known to lead to cerebrovascular events in the elderly, and so their use in this population should be minimized. They also appear to increase the rate of mortality from all conditions in this population for unknown reasons. Finally, while the development of extrapyramidal side effects and tardive dyskinesia is greatly reduced in this class compared to the older typical antipsychotics, it is not nonexistent. Again, it appears some are more likely than others to cause extrapyramidal problems, particularly Risperdal (risperidone). Risperdal (risperidone) also can elevate prolactin, which has a number of adverse consequences, including breast growth, lactation, and decreased libido.

Terms:

Extrapyramidal - the parts of the brain responsible for static motor control. The basal ganglia are part of this system. Deficits in this system result in involuntary movement disorders.

Antipsychotic medications - affect these areas, leading to extrapyramidal side effects, which include muscle spasms (dystonias), tremors (Parkinson’s), shuffling gait, restlessness (akathisia), and tardive dyskinesias.

Tardive dyskinesia - a late-onset involuntary movement disorder, often irreversible, typically of the mouth, tongue, or lips, and less commonly of the limbs and trunk. These movements are a consequence of long-term antipsychotic use but are less commonly observed with the newer, atypical antipsychotics.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs have been on the market since the introduction of Prozac in the late 1980s. Numerous studies have attempted to link them to long-term dangers such as cancer or other medical conditions aside from their psychological effects. None of these studies has yet held up to any scrutiny. All of the studies linking SSRIs to suicidal behavior analyze data at the beginning of treatment and most likely represent an unidentified side effect that can be associated with suicidal behavior. Such side effects could be increasing anxiety and insomnia or an extrapyramidal side effect that causes patients to become uncomfortably restless (akathisia).

Another factor that may be involved is the improvement in energy levels that often occurs before an improvement in mood, which may result in increased motivation and energy to act on suicidal desires. This is why close monitoring during the initial phase of treatment with these medications is imperative.

Terms:

Akathisia - a subjective sense of inner restlessness resulting in the need to keep moving.

Objectively, restless - movements or pacing may be signs of akathisia.

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(43) Bipolar Disorder

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When I was 17 my mother decided she’d had it and threw me out. At the time I hated her for it, but now I can’t honestly blame her. Back then, she hasn’t heard before about bipolar disorder, all the more couldn’t recognize that these were typical bipolar symptoms. Frightened, vulnerable and sick with bipolar disorder, I headed into the east end of Los Angeles and lived on the streets for a year. It was hell. I was homeless and hungry. It was extremely difficult to find shelter and food. I was utterly lost. I got busted for possession of marijuana and for prostitution. I had to sell my body. Using drugs, illicit sex and a lack of self-respect are all symptoms of bipolar disorder.

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BD43

What is metabolic syndrome and how does it relate to mood stabilizers?

If you have three or more of the following you are diagnosed with metabolic syndrome:

• A waistline of 40 inches or more for men and 35 inches or more for women (measured across the belly)

• A blood pressure of 130/85 mm Hg or higher

• A triglyceride level above 150 mg/dl

• A fasting blood glucose (sugar) level greater than 100 mg/dl

• A high-density lipoprotein level (HDL) less than 40 mg/dl (men) or less than 50 mg/dl (women)

This syndrome is important to mental health for the following reasons. Metabolic syndrome, more often than not, is caused by obesity. Bipolar disorder may increase the risk of obesity and metabolic syndrome due to changes in energy related to mood variability.

The severity and chronicity of bipolar disorder may also affect the incidence of obesity. The number of previous episodes is positively correlated with being overweight or obese. The greatest gain in weight for bipolar patients is during the acute phase of their treatment. Obese individuals tend to have a more severe and intractable type of illness. There is some preliminary evidence that treating severe obesity may improve mood, at least depression. At Danbury Hospital in Connecticut, the bariatric surgery department has been following its patients for several years now and documenting the changes in medication as a result of weight loss. They have found that with the reduction in weight, and the resulting reduction in fasting blood sugars, triglycerides, and cholesterol, a significant number of the patients eventually no longer require antidepressant medication. It is not clear if the same effect occurs with bipolar patients, as there are just too few of these patients in the program to have any reliable numbers.

Finally, the medications used to stabilize mood may cause weight gain and/or metabolic syndrome. It appears that just about all the medications used to treat bipolar disorder, old and new, lead to weight gain. Of the atypical antipsychotics, the medications that cause the most weight gain, in order of most significant to almost negligible, include Clozaril (clozapine), Zyprexa (olanzapine), Risperdal (risperidone), Seroquel (quetiapine), Geodon (ziprasidone), and Abilify (aripiprazole). These medications have also been implicated in elevated fasting blood sugars, elevated cholesterol and triglycerides, and rarely the development of diabetes (again in descending order).

Although these two risks are related, it is possible to develop any one of them without the others. The traditional mood stabilizers lithium and Depakote (valproate) can also cause weight gain, but have not been shown to cause metabolic syndrome. In fact, some evidence suggests that adding Depakote (valproate) to Risperdal (risperidone) lowers the cholesterol in Risperdal (risperidone) users. These weight changes are most dramatic in thinner individuals. But being overweight prior to treatment conveys its own risks, particularly the risks of precipitating or worsening metabolic syndrome. You should work with both your internist and psychiatrist to choose medications that are most effective with the fewest side effects.

Strategies you can take to reduce the chances of weight gain during treatment include changing your diet, increasing exercise, and/or choosing medications less associated with weight gain. These include mood stabilizers such as Trileptal (oxcarbamazepine) or Lamictal (lamotrigine), or the lowest-risk atypical antipsychotics such as Geodon (ziprasidone) or Abilify (aripiprazole). In addition, a combination of medications can be taken that can either reverse or reduce the risk of weight gain. These combinations include a variety of off-label strategies such as adding Topamax (topiramate), Symmetrel (amantadine), metformin, or Pepcid to Zyprexa (olanzapine). All of these strategies carry a degree of risk, and to date none have proven to be universally effective.

Why did my doctor prescribe an antipsychotic for me when I am just depressed?

Antipsychotic medications are often prescribed for patients suffering from psychotic symptoms resulting from their depression. Such symptoms often revolve around false beliefs that the patient deserves some horrible punishment for a minor transgression the patient believes to be a major sin or crime. Antipsychotics specifically target those symptoms, thus relieving patients of those painful thoughts and feelings. With the introduction of newer antipsychotic medications, however, their use as augmenting agents to antidepressants even in the absence of psychosis has become a new option for psychiatrists.

The newer antipsychotic medications, called atypical antipsychotics or second-generation antipsychotics (SGAs), were developed because of increasing concern regarding the risk of developing a severe, potentially irreversible movement disorder known as tardive dyskinesia. Patients suffering from mood disorders are at greater risk for developing this movement disorder than patients who suffer primarily from psychotic disorders.

SGAs have reduced this risk dramatically. They are, as a result, generally safer to use than their predecessors, although recently there have been growing concerns about their metabolic effects on the body, including the potential for weight gain, increased blood sugar, and increased cholesterol and lipids.

Despite these concerns, they remain an effective strategy when patients are showing only a partial response to their antidepressant medication or have a history of bipolar disorder and need medication to prevent the possibility of mania while undergoing treatment with an antidepressant medication.

How does generic medication differ from trade names?

The generic name of a medication is the international scientific name for the molecule that constitutes the active form of the medication. The company that develops the medication applies for a patent and obtains exclusive rights to sell the medication. They then give the medication a trade name. This trade name can change from country to country and from its intended use. For example, the medication with the generic name paroxetine is marketed under the trade name Paxil in the United States and Seroxat in the United Kingdom. The medication with the generic name bupropion is used as an antidepressant under the trade name Wellbutrin and as a smoking cessation medication under the name Zyban. The medication with the generic name fluoxetine is used under the trade name Prozac as an antidepressant and as Sarafem, a medication prescribed by obstetricians, for women suffering from premenstrual symptoms. Once a medication goes off patent, other companies obtain the right to make it and sell it. At this point generic forms of the medication that may be less expensive become available. These medications are sold under their generic names. As physicians first know the original form of the medication by its trade name, the physicians often continue to write prescriptions under that name. By law pharmacies must fill the prescription with the less-expensive form of the medication unless the physician specifically indicates to the pharmacy not to substitute. As a result the filled prescription will come back to the patient under the generic name rather than the trade name.

Are there differences between generic medications and medications under the trade name? The active ingredients of the medication are identical. The “fillers” or inactive ingredients making up the rest of the medication may differ. There may also be more percentage variations between the amounts of active ingredients from pill to pill in generic medications than in trade medications as the requirements for quantity control are more stringent with trade medications than with generic medications. Generic medications can vary by +/- 20% in bioavailability (the amount of medication that reaches the bloodstream).

Different companies can manufacture generics so each time you get a refill on a generic you may get a different one with different bioavailability. For many medications, these differences are so minute as to be negligible, and with repeated dosing the differences cancel each other out. However, some drugs used to treat bipolar disorder, such as Depakote, Depakot ER, Eskalith, Lithobid, and Equetro have a narrow therapeutic index (NTI). With NTI drugs, small variances in the blood levels may cause changes in the effectiveness or toxicity of that drug. Many insurance plans will cover both the brand name drugs and the generics, although some drugs have no generic substitution. Physicians may indicate “dispense as written” to ensure a brand name drug is dispensed by the pharmacist.

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(44) Bipolar Disorder

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Are mood stabilizers prescribed for reasons other than bipolar disorder?

The term mood stabilizer typically refers to a medication with antimanic properties and is actually a misnomer. Most psychoactive medications have multiple effects and the decision to label a particular medication a mood stabilizer, an antidepressant, an anticonvulsant, an antipsychotic, or an anxiolytic is often as much a matter of marketing as it is due to the drug’s clinical effects. The newer class of psychotropic medications known as atypical antipsychotic medications, for example, were developed and designed as antischizophrenic medications. Only later were they tested and marketed as mood stabilizers.

Because of their relatively benign safety profile compared with their earlier counterparts (Haldol) (haloperidol) and chlorpromazine, for example), however, they have been used as both antianxiety medications and sedative/hypnotic medications. More recently they are being studied for use in both unipolar and bipolar depression.

Thus, mood stabilizers have multiple properties that are utilized by different physicians to target specific symptoms with which their patients present. For example, neurologists have long been using mood stabilizers that are anticonvulsants to treat epilepsy, but also to prevent migraine headaches and other pain syndromes. Many patients with panic disorder who do not respond to SSRIs (e.g., Sarafem [fluoxetine]) will respond to the anticonvulsant medication valproic acid. But mood stabilizers have been used in the treatment of other anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. The atypical antipsychotics have been found to be especially useful in severe obsessive-compulsive disorder in which the obsessions are intractable. Seroquel (quetiapine) has been found to be especially useful in managing insomnia associated with drug and alcohol dependency and psychosis in patients suffering from Parkinson’s disease, and it has been used as an alternative to the benzodiazepines in managing anxiety. .

Conditions for which mood stabilizers are utilized

Mood disorders

Anxiety disorders

Impulse control disorders

Sleep disorders

Seizure disorders

Migraines

I have been diagnosed with bipolar disorder and anxiety.How is the combination of conditions treated?

Anxiety is a condition that commonly occurs with bipolar disorder, particularly in the manic phase of the illness, but can also occur in the depressive phase or co-occur as an independent condition. The easiest way to think about this is that if you only have anxiety in the manic or depressive phase of the illness and it abates when your mood stabilizes, then it is a symptom of the bipolar disorder and not an independent condition.

The type of anxiety associated with mania is on a level far more extreme than generalized anxiety. People commonly describe it as a restless energy that will not allow them to sit still. It is often accompanied by irritability and racing or disorganized thoughts. Sometimes the anxiety results because your ambitious grandiose schemes are being thwarted by others who cannot understand the vast rewards completion of such schemes will bring.

Some anxiety conditions, such as social phobia, panic disorder, and generalized anxiety disorder, can cycle with your moods, essentially abating during the hypomanic or manic phase but returning during euthymia and even worsening during the depressive phase. The treatment for anxiety in the context of bipolar disorder is tricky. The SSRIs are a very useful treatment for many anxiety disorders but are less than ideal in persons who suffer from both anxiety and bipolar disorder.

The benzodiazepines, which can be very beneficial in aborting panic attacks, are also tricky because the rate of alcoholism and drug abuse is high among bipolar individuals.

The first task in treatment is to control the bipolar disorder as best as possible. Fortunately, many of the anticonvulsant agents affect GABA, the major neurotransmitter implicated in many anxiety disorders, and therefore they can have anxiolytic and antipanic effects independent of their mood-stabilizing properties.

If the anxiety abates with mood stabilization you are in luck. If not, the problem is a bit trickier. Some anxiety conditions, such as posttraumatic stress disorder and obsessive-compulsive disorder, respond preferentially to SSRIs, and SSRIs are clearly trickier to use in bipolar disorder, as mentioned previously. If the symptoms are generally in check, cognitive-behavioral therapy is the treatment of choice. If an SSRI is warranted, remaining on an antimanic agent is imperative prior to its initiation. A combination of therapy and medication is typically the best treatment approach for a variety of anxiety disorders, such as generalized anxiety disorder, panic disorder, social anxiety disorder, and obsessive-compulsive disorder.

Scott’s comments:

This was my diagnosis exactly. My anxiety is being treated with Klonopin, which I find highly effective. Combined with my bipolar medication, I feel like normal now. The behaviors that I used to exhibit are no longer part of my persona, but memories of days past. The thought of trying to tough it out with both bipolar disorder and anxiety disorder just seems way too hard when modern medicine is available to treat these conditions so specifically. Better living through chemistry, indeed.

My spouse is drinking a lot of alcohol lately. My friend thinks he might be self medicating. What does that mean?

Individuals with a mood disorder may abuse alcohol or drugs in a misguided effort to feel better. In the case of depression, alcohol can initially give the impression of improving one’s mood, but in actuality, alcohol is a depressant. Likewise, use of drugs to get “high” is usually followed by a “crash” during which the mood becomes sad or despondent. During mania, both poor impulse control and recklessness can result in alcohol and/or drug abuse. Such substances, however, serve to further exacerbate the condition and can contribute to a crash into depression.

Depression can sometimes be caused by the alcohol or drug abuse itself and will remit when abstinence is achieved. Often depression precedes the alcohol or drug use, and people turn to these substances in an effort to feel better. Typically though, feeling better really just means being “numb” or deadened to the depressed feelings. Treatment of the depression and/or mania may result in achievement of abstinence. This of course will depend on the stage of substance abuse. If the individual has become dependent on (addicted to) the alcohol or drugs, then concordant substance abuse treatment will likely be necessary as well. As long as the person is addicted to alcohol or drugs, recovery from bipolar disorder will be limited.

In fact, substance abuse is a problem that needs to be considered if someone is refractory to treatments for bipolar disorder. Seeing a person who specializes in treatment of addictions would also be helpful as there are different forms of therapeutic interventions often needed in persons who have addiction. In addition, there are specialized treatment programs for persons with both bipolar disorder and substance abuse

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(45) Bipolar Disorder

What does a Bipolar Disorder episode look like?

Bipolar Disorder and Addiction

BD45

Why is my doctor telling me I need treatment for my addiction when I thought treating the depression would solve my problem?

Patients with a combination of addiction and depression are at higher risk for suicide, homicide, poor compliance, relapse, and greater hospitalization rates. Although there is some evidence to support the concept that many patients use substances to “self-medicate” an underlying depression, there is no evidence that antidepressant medication leads to abstinence. Although the “self-medication hypothesis” may seem right for some individuals, once an addiction develops it takes on a life of its own. It is unlikely that medicating it away can conquer addiction.

Also, if you continue to use drugs or alcohol while receiving antidepressant medication, they render antidepressant medication essentially ineffective. Thus depression cannot be effectively treated without also treating the addiction. However linked they may have been in their origins, they are now separate entities that both require treatment in order for you to return to health.

How are alcoholism and bipolar disorder connected?

Bipolar disorder and alcoholism do co-occur at higher than-expected rates. No one knows why but it appears, surprisingly, that they are not genetically linked. Bipolar men who are alcoholics often had a family history of alcoholism when compared with nonalcoholic bipolar men. Alcoholism among bipolar women, however, was not associated with a family history of alcoholism.

Instead, their addiction often stemmed from anxiety and depression. Bipolar women have a higher risk of developing alcoholism than non-bipolar women. The rate in bipolar women for alcoholism is 29%, and in bipolar men it is 49%.

More importantly, alcohol, cocaine, heroin, PCP, and marijuana can all cause mood swings that make everyone using these drugs suspect of having a mood disorder in general and bipolar disorder more specifically. When these patients are hospitalized psychiatrically as a result of an impulsive, potentially dangerous behavior in the context of their drug and alcohol abuse, the likelihood of their being discharged on a “cocktail” of psychiatric medications with a diagnosis of bipolar disorder is high. With average lengths of stay in a psychiatric hospital of about a week the accuracy of such a diagnosis is suspect at best.

The proof is not even in the pudding, because complicating the picture is the fact that the medications one is discharged on are symptom and not diagnostic specific.

Therefore, although one’s mood may stabilize with an anticonvulsant agent or antipsychotic that does not mean one has bipolar disorder. Unfortunately, the pitfall inherent in the diagnosis is that all too often these patients and their families focus entirely on the bipolar diagnosis, attributing continued relapse into drugs and alcohol to bipolar disorder while doing nothing to get treatment for substance or alcohol abuse. Alcohol and drugs of abuse worsen bipolar symptoms and go further toward explaining the mood swings than vice versa. More likely, any mood swings stand a far better chance of improvement from abstinence than from any psychotropic medication offered.

Are individuals with bipolar disorder at risk for drug abuse?

Alcohol and drug abuse is very common among people with bipolar disorder. The most common co-occurring illnesses with bipolar disorder are substance abuse disorders, with up to 60% of patients with bipolar disorder having substance-related problems. Substance abuse can make bipolar disorder more severe and worsen the course of the disease by exacerbating symptoms or precipitating episodes. Such comorbidity may result from the self-medication of mood disorder symptoms, or mood symptoms may be induced by substance abuse. The risk of comorbid substance abuse may be increased by family history of substance use, an early age of onset of bipolar disorder, and the presence of mixed episodes. Treatment for co-occurring substance abuse, when present, is an important part of the overall treatment plan. The diagnosis of bipolar disorder should not be made in the presence of active substance use, as many illicit drugs (and the rapid withdrawal from them) can cause symptoms of mania (and subsequent depression). Ideally the substance of use is discontinued so that a baseline of functioning can be assessed. Symptoms should dissipate if due to an ingested substance. If substance abuse persists, treatment for presumed bipolar disorder may be initiated if co-occurring substance abuse treatment is obtained. Even if self-medication of symptoms was the reason illicit substance use was initiated, once abuse or dependence has set in, the problem will require separate treatment.

Since returning from active duty overseas, my husband is having rageful episodes, is irritable, is suspicious of others and complains of racing thoughts at night. Is he bipolar?

Active duty can be a precipitating stressor for many mental disorders. As part of any evaluation, various diagnoses are considered because of overlapping symptoms.A common combat casualty for many soldiers returning from war is posttraumatic stress disorder (PTSD). Symptoms of PTSD can look very much like a mood disorder, and in fact untreated PTSD often results in development of depression and substance abuse. In some studies as many as 52% of subjects develop alcohol abuse or dependence and 47% develop depression. In a person who is at higher risk for bipolar disorder, it is certainly plausible that the first episode would occur following as stressful an event as active duty in combat. In fact, in a recent NIMH-funded study, a high percentage of persons diagnosed with bipolar disorder also exhibited symptoms of PTSD. Symptoms of PTSD may look like bipolar disorder, however.

PTSD is associated with three primary symptoms that persist for longer than a month after a traumatic event:

• Re-experiencing, such as flashbacks or nightmares or intense memories

• Hyperarousal, such as jumping at noises one used to ignore

• Numbing, such as an inability to feel pleasure and a tendency to isolate

With re-experiencing, there are recurrent, intrusive thoughts and images in the mind. The patient may exhibit behavior as if the events were recurring, and intense psychological distress can occur. Re-experiencing can result in irritability and agitation. Racing thoughts may actually be the recurrent memories and ruminations. Symptoms of hyper arousal include difficulty sleeping, outbursts of anger, difficulty concentrating, and hyper vigilance. Symptoms of numbing include detachment and avoidance, which can look like depression. The cluster of symptoms can thus look very much like bipolar disorder. In a recent study of U.S. soldiers returning from Iraq, about 16% said they were experiencing symptoms of depression and anxiety.

Although their symptoms are likely to be caused by PTSD, it is important to rule out bipolar disorder because the treatment for PTSD is typically an antidepressant, which would not be indicated during an acute hypomanic or manic episode. The sad truth is, though, that many if not most soldiers will not admit to having a problem or seek help. They have been trained to “suck it up,” and they consider any admission of emotional problems related to their duty as an admission of weakness in the face of their responsibility.

The earlier your spouse gets into treatment, the better the chance for a positive outcome.

Terms:

Re-experiencing - the phenomenon of having a previous lived experience vividly recalled and accompanied by the same strong emotions one originally experienced.

Hyperarousal - a heightened state of alertness to external and internal stimuli, often results in sleep disturbance, problems concentrating, hypervigilance, and exaggerated startle response. Typically seen in posttraumatic conditions.

Numbing - the psychological process of becoming resistant to external stimuli so that previously pleasurable activities become less desirable.

Ruminations - obsessive thinking over an idea or decision.

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