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DRUGS FOR MENTAL ILLNESS, a review

Three Articles:

 

MAJOR  DEPRESSION

 

     MANIC  DEPRESSIVE  ILLNESS

 

          SCHIZOPHRENIA  FACTS
 

Major Depression

If a depressed mood is accompanied by several of the following problems has been present for at least several weeks, and a careful history, physical exam, and lab tests have ruled out specific causes of depression, true primary depression is probably the diagnosis. The problems are sadness that impairs normal functioning, difficulty concentrating, low self-esteem, guilt, suicidal thoughts, extreme fatigue, low energy level or agitation, sleep disturbances (increased or decreased), or appetite disturbance (increased or decreased) with associated weight change. Since suicidal thoughts and attempts often characterize depression, the possibility of suicide using antidepressant drugs has to be kept in mind and only a small number of pills prescribed at one time. Another way of describing the pervasive nature of this kind of severe depression is that the person displays, and relates if asked, a sense of helplessness, hopelessness, worthlessness and uselessness . . . as well as intense feelings of guilt over real or imagined short-comings or indiscretions.

It is important to rule out other causes of depression because people who appear depressed may have a thyroid disorder, a type of cancer, such as pancreatic, bowel, brain, or lymph node (lymphoma), viral pneumonia, or hepatitis. In addition, there is evidence that people who have had a stroke or who have Parkinson's disease or Alzheimer's disease may become depressed and, in some cases, may respond to antidepressant drugs.

According to data from the National Institute of Mental Health, nearly 4 percent of people age 25 to 44 (about 3 million people) have had a major depression recently, although there are significant numbers of younger and older people who also have serious depression.

 

Everyone with the kind of severe depression described above should be evaluated by a mental health professional to determine what kind of psychotherapy would best supplement the antidepressant drugs that are going to be used.

The decision as to which drug is best will depend, in part, on choosing one with the fewest adverse effects, since most classes of antidepressants are equally effective on an aggregate or group basis.  However, any given individual may respond to one kind of antidepressant much better than to another. If depression has occurred previously and responded to one of the drugs without too many adverse effects, that would be the best one to try first. Otherwise, this chart  compares the common adverse reactions of the antidepressants.

The Main Risks of Antidepressant Drugs

The five most common groups of adverse effects are anticholinergic, sedative, hypotensive (blood-pressure-lowering), effects on heart rate or rhythm and sexual dysfunction.

Anticholinergic Effects

Older adults are especially sensitive to the anticholinergic effects of tricyclic antidepressants. Mental effects that can result are confusion, delirium, short-term memory problems, disorientation, and impaired attention. The are also physical effects that can results from using drugs with anticholinergic effects such as dry mouth, constipation, difficulty urinating (especially for men with enlarged prostate), blurred vision, decreased sweating with increased body temperature, sexual dysfunction, and worsening of glaucoma.

Sedative Effects

If sleep disorder is a consequence of severe depression, the "adverse effect" of sedation may be useful as long as it does not produce too much sedation, with the risk of falling. This is an important consideration especially in people who already have some impairment of thinking, increased confusion, disorientation, and agitation.

Hypotensive Effects: lowering of blood pressure to levels that are too low

Orthostatic (postural) hypotension, or the fall in blood pressure that occurs when someone stands up suddenly, is a common adverse effect of antidepressants, especially in older adults. It can be even more troublesome if the person is already at increased risk for this problem because he or she is taking other drugs to treat high blood pressure. As a result of such a drug-induced drop in blood pressure, falls that result in injury, heart attacks, and strokes can occur. For this reason, before starting treatment with one of these antidepressants, blood pressure should be taken both in the lying position and after standing for two minutes. This should be repeated after using the drug for several weeks.

Drug-induced parkinsonism

Like the antipsychotic drugs, many antidepressants can also cause drug-induced parkinsonism. Drug-induced parkinsonism involves the following symptoms: difficulty speaking or swallowing; loss of balance; mask-like face; muscle spasms; stiffness of arms or legs; trembling and shaking; unusual twisting movements of body.

Effects on heart rate and rhythm

These drugs can cause the heart to speed up. They can also cause a slowing down in the conduction of electricity through the heart, which is especially dangerous if someone already has heart block. For this reason, a baseline electrocardiogram should be taken before starting any antidepressant therapy.

Mania induced by serotonin reuptake inhibitors

All currently available antidepressant drugs appear able to induce hypomanic and manic reactions. This is a serious concern for people taking the serotonin reuptake inhibitor group of antidepressants which includes the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine but also the antidepressants such as nefazodone that have a combined effect on serotonin and norepinephrine reuptake. This reaction can be severe having psychotic features or requiring patients to be secluded for extreme agitation.

Gastrointestinal adverse effects

Gastrointestional (GI) adverse effects, particularly nausea and diarrhea, are seen more frequently with the newer SSRI antidepressants than the older tricyclic problems.

Sexual Dysfunction

All antidepressants medications have been associated with varying degrees of sexual dysfunction in both men and women. Sexual dysfunction appears to be more common with the newer SSRI antidepressants than with the older tricyclic drugs.

The drugs appearing in this chart (comparing the common adverse reactions of antidepressants) are arranged in alphabetical order by generic name with the brand appearing in parenthesis in upper case letters. For example, if you were comparing the common adverse effects of amitriptyline (ELAVIL) to fluoxetine (PROZAC) you would see that the anticholinergic and sedative effects of amitriptyline are both strong while these effects are absent with fluoxetine. On the other hand nausea and diarrhea are more frequent with fluoxetine than amitriptyline. Amitriptyline has a moderate effect in causing low pressure when standing while fluoxetine does not. Both drugs cause sexual dysfunction, but this is more frequent with SSRI drugs like fluoxetine than with tricyclic antidepressants like amitriptyline. These adverse effects must be balanced with the fact that these drugs are equally beneficial in patients with severe depression.

Drug-induced depression

Ironically, one of the kinds of depression that should not be treated with drugs is depression caused by other kinds of drugs. If someone is depressed and the depression started after beginning a new drug, it may well be drug-caused. Commonly used drugs known to cause depression include the following:

Barbiturates such as phenobarbital
Tranquilizers such as diazepam (VALIUM) and triazolam (HALCION)
Heart drugs containing reserpine (SER-AP-ES and others)
Beta-blockers such as propranolol (INDERAL)
High blood pressure drugs such as clonidine (CATAPRES), methyldopa (ALDOMET), and prazosin (MINIPRESS) Drugs for treating abnormal heart rhythms such as disopyramide (NORPACE)
Ulcer drugs such as cimetidine (TAGAMET) and ranitidine (ZANTAC)
Antiparkinsonians such as levodopa (LARODOPA) and bromocriptine (PARLODEL)
Corticosteroids such as cortisone (CORTONE) and prednisone (DELTASONE)
Anticonvulsants such as phenytoin (DILANTIN), ethosuximide (ZARONTIN), and primidone (MYSOLINE)
Antibiotics such as cycloserine (SEROMYCIN), ethionamide (TRECATOR-SC), ciprofloxacin (CIPRO) and metronidazole (FLAGYL)
Diet drugs such as amphetamines (during withdrawal from the drug)
Painkillers or arthritis drugs such as pentazocine (TALWIN), indomethacin (INDOCIN), and ibuprofen (MOTRIN, ADVIL)
The acne drug isotretinoin (ACCUTANE)
Other drugs including metrizamide (AMIPAQUE), a drug used for diagnosing slipped discs, and disulfiram (ANTABUSE), the alcoholism treatment drug.

The remedy for this kind of depression is to reduce the dose of the drug or stop it altogether if possible. If necessary, switch to another drug that does not cause depression.

Another major cause of drug-induced depression is alcoholism, the treatment of which is difficult.


 

Manic Depressive Illness

(also known as Bipolar Disorder)

Individuals diagnosed with manic-depressive illness, or bipolar disorder, have mood swings that alternate from periods of severe highs (mania) to extreme lows (depression). These mood swings, which are out of proportion or totally unrelated to events in a person's life, affect thoughts, feelings, physical health, behavior, and functioning.

 

Manic-depressive illness is a neurobiological brain disorder that affects approximately 1.3 million Americans today, 0.5 percent of the population. While manic-depressive illness usually begins in adolescence or early adulthood, it can sometimes start in early childhood or as late as age 40 or 50.

Generally, people with manic-depressive illness consult between three to four doctors and spend more than eight years seeking treatment before they receive a correct diagnosis.

The average person has four episodes of mania or depression during the first 10 years of the illness. Men are more likely to start with a manic episode, and women are more likely to begin with a depressive episode.

Symptoms of Manic Depressive Illness

 

While no single pattern of symptoms fits every individual with manic-depressive illness, there are four distinct types of mood episodes that can occur over the course of the illness, including:

Mania (manic episode) often begins with a pleasurable sense of heightened energy, creativity, and social ease; feelings that without proper medical treatment can quickly escalate out of control into a full-blown manic episode. People experiencing mania typically lack self-awareness, deny anything is wrong, and angrily blame anyone who points out a problem. In addition to feeling unusually "high," euphoric or irritable, the person also may exhibit symptoms such as:

• Needing little sleep yet having great amounts of energy;

• Talking so fast that others can't follow the person's thinking;

• Having racing thoughts;

• Being so easily distracted that the individual's attention shifts between many topics in just a few minutes; and

• Having an inflated feeling of power, greatness or importance; and doing reckless things without concern about possible bad consequences, such as spending too much money, inappropriate sexual activity, making foolish business investments.

Hypomania (hypomanic episode) is a milder form of mania with similar yet less severe symptoms and less overall impairment. In hypomania, for example, the individual may have an elevated mood, feel better than usual, and be more productive. These episodes often feel good, and the quest for hypomania may even cause people to stop taking their medication.

Depression (major depressive episode) takes away the capacity to experience pleasure, and causes profound sadness and irritability, changes in sleep patterns, a decrease in appetite, an inability to concentrate, low self-esteem, and thoughts of suicide. Severe depressions also may include hallucinations or delusions.

Mixed Episode is perhaps the most disabling since an individual can experience both mania and depression simultaneously or at different times throughout the day.

Treating Manic-Depressive Illness

While there is no cure for manic-depressive illness, it is a highly treatable disease. In fact, according to the National Advisory Mental Health Council, the treatment success rate for manic-depressive illness is a remarkable 80 percent.

 

It is important to diagnose and treat manic-depressive illness as early as possible to help people avoid or reduce frequent relapses and re-hospitalizations. Several promising, large-scale studies suggest early intervention may forestall the worst long-term outcomes of this devastating brain disorder.

 

Individuals experiencing mania often lack self-awareness and do not recognize that they are ill and require treatment in the hospital to prevent self-destructive, impulsive, or aggressive behavior. Hospital stays can be as brief as two weeks and as long as six months.

The two most important types of medication used to control the symptoms of manic-depressive illness are mood stabilizers and antidepressants.

 

Mood Stabilizers, the mainstay of long-term preventive treatment for both mania and depression, are used to improve symptoms during acute manic, hypomanic, and mixed episodes; they also may reduce symptoms of depression. The most widely used mood stabilizers include lithium (ESKALITH, LITHOBID, LITHONATE, and other brands), valproate (used as divalproex or DEPAKOTE), and carbamazepine (TEGRETOL).

 

About one in three people will be completely free of symptoms by taking mood stabilizing medications for life.   {This is the same as for those receiving a placebo, for about one-third will without drugs recover from a depression episode—jk.}

 

In conjunction with the mood stabilizers, antianxiety medications such as lorazepam (ATIVAN) and clonazepam (KLONOPIN) and antipsychotic drugs such as haloperidol (HALDOL) and perphenazine (TRILAFON) are used for insomnia, agitation, or other symptoms, during a manic phase.

Antidepressants are given together with mood stabilizers to prevent an "overshoot" from occurring in the patient, for if used on their own in the treatment of bipolar disorder, antidepressants can push moods up too high causing hypomania, mania, or rapid cycling. Most experts consider the following two types of antidepressants to be the most effective for bipolar patients: bupropion (WELLBUTRIN) or selective serotonin reuptake inhibitors such as: fluoxetine (PROZAC); fluvoxamine (LUVOX); paroxetine (PAXIL), and sertraline (ZOLOFT). There are many other choices if these do not work, or if they cause unpleasant adverse effects, including: mirtazapine (REMERON), monoamine oxidase inhibitors such as phenelzine (NARDIL) and tranylcypromine (PARNATE); nefazodone (SERZONE); tricyclic antidepressants such as amitriptyline (ELAVIL), desipramine (NORPRAMIN), imipramine (TOFRANIL), nortriptyline (PAMELOR); and venlafaxine (EFFEXOR).

 

Suicide is the number one cause of premature death among people with manic-depressive illness, with 15 percent to 17 percent taking their own lives as a result of negative symptoms that come from untreated illness. The extreme depression and psychoses that can result due to lack of treatment are the usual culprits in these sad cases. These suicides rates can be compared to that of the general population, which is somewhere around one percent.   

 

 

 

Schizophrenia Facts

Schizophrenia interferes with a person’s ability to think clearly, manage emotions, make decisions, and relate to others. Specific abnormalities that can be noted in individuals with schizophrenia include:

• delusions and hallucinations;

• alterations of the senses;

• an inability to sort and interpret incoming sensations, and an inability therefore to respond appropriately;

• an altered sense of self; and changes in emotions, movements and behavior.

Schizophrenia is a neurological brain disorder that affects 2.2 million Americans today, or almost one percent of the population. Schizophrenia can affect anyone at any age, but most cases develop between ages 16 and 30.

Symptoms of Schizophrenia

In healthy people, the brain functions in such a way that incoming stimuli are sorted and interpreted, followed by a logical response (e.g., saying "thank you" after a gift is given, realizing the potential outcome of arriving late to work, etc.). Conversely, the inability of patients with schizophrenia to sort and interpret stimuli and select appropriate responses is one of the hallmarks of the disease.

The symptoms of schizophrenia are generally divided into three categories, including positive, disorganized, and negative symptoms.

 

Positive, or "psychotic" symptoms, include delusions, and hallucinations which occur because the patient has lost touch with reality in certain important ways. Delusions cause the patient to believe that people are reading their minds or plotting against them, that others are secretly monitoring and threatening them, or that they can control other people’s thoughts. Hallucinations cause people to hear or see things that are not there. Approximately three-fourths of individuals with schizophrenia will hear voices (auditory hallucinations) at some time during their illness.

 

Disorganized thinking, speech, and behavior affect most people with this illness. For example, people with schizophrenia sometimes have trouble communicating in coherent sentences or carrying on conversations with others; move more slowly, repeat rhythmic gestures or make movements such as walking in circles or pacing; and have difficulty making sense of everyday sights, sounds and feelings.

 

Negative symptoms include emotional flatness or lack of expression, an inability to start and follow through with activities, speech that is brief and lacks content, and a lack of pleasure or interest in life. "Negative" does not, therefore, refer to a person’s attitude, but to a lack of certain characteristics that should be there.

Diagnosing Schizophrenia

To be diagnosed with schizophrenia, a patient must have psychotic, "loss-of-reality" symptoms for at least six months and show increasing difficulty in functioning normally. Before the six-month period is reached, the person is diagnosed as having a schizophreniform disorder.

 

Prior to a medical diagnosis, it is critically important that a doctor rule out other problems that may mimic schizophrenia, such as psychotic symptoms caused by the use of drugs or other medical illnesses; major depressive episode or manic episode with psychotic features; delusional disorder (no hallucinations, disorganized speech or thought or "flattened" emotions) and autistic disorder or personality disorders (especially schizotypal, schizoid, or paranoid personality disorders). Schizoaffective disorder is a diagnosis used to indicate that the person has an illness with a mix of symptoms of both schizophrenia and bipolar disorder.

 

Although the cause of schizophrenia has not yet been identified, recent research suggests that schizophrenia is linked to abnormalities of brain chemistry and brain structure. Genes play some role, but the magnitude of that role remains to be ascertained. Abnormalities of neurotransmitters (e.g., dopamine, serotonin) and viruses also are under investigation. The brain changes in some cases are suspected to date to childhood. Brain-imaging technology has demonstrated that schizophrenia is as much an organic brain disorder, as is Multiple Sclerosis, Parkinson’s or Alzheimer’s disease.

Treating Schizophrenia

While there is no cure for schizophrenia, it is a highly treatable disorder. In fact, according to the National Advisory Mental Health Council, the treatment success rate for schizophrenia is comparable to the treatment success rate for heart disease.

 

It is important to diagnose and treat schizophrenia as early as possible to help people avoid or reduce frequent relapses and re-hospitalizations. Several promising, large-scale studies suggest early intervention may forestall the worst long-term outcomes of this devastating brain disorder.

People who experience acute symptoms of schizophrenia may require intensive treatment, sometimes including hospitalization. Hospitalization is necessary to treat severe delusions or hallucinations, serious suicidal inclinations, severe problems with drugs or alcohol and the inability to care for oneself.

 

It is critical that people with schizophrenia stay in treatment even after recovering from an acute episode. About 80 percent of those who stop taking their medications after an acute episode will have a relapse within one year, whereas only 30 percent of those who continue their medications will experience a relapse in the same time period.

 

Medication appears to improve the long-term prognosis for many people with schizophrenia. Studies show that after 10 years of treatment, one-fourth of those with schizophrenia have recovered completely, one-fourth have improved considerably, and one-fourth have improved modestly. Fifteen percent have not improved, and 10 percent are dead.  {The one-fourth, cure rate is about equal to those who are not treated—jk}

 

Individuals with schizophrenia die at a younger age than do healthy people. Males have a 5.1 times greater than expected early mortality rate than the general population, and females have a 5.6 times greater risk of early death. Suicide is the single largest contributor to this excess mortality rate, which is 10 to 13 percent higher in schizophrenia than the general population.

 

Suicide is, in fact, the number one cause of premature death among people with schizophrenia, with an estimated 10 to 13 percent killing themselves. The extreme depression and psychoses that can result due to lack of treatment are the usual culprits in these sad cases. These suicides rates can be compared to that of the general population, which is somewhere around one percent. Other contributors to excess mortality include:

 

Accidents: Although individuals with schizophrenia do not drive as much as other people, studies have shown that they have double the rate of motor vehicle accidents per mile driven. A significant but unknown number of individuals with schizophrenia also are killed as pedestrians by motor vehicles.

 

Diseases: There is some evidence that individuals with schizophrenia have more infections, heart disease, type II (adult onset) diabetes, and female breast cancer, all of which might increase their mortality rate. Individuals with schizophrenia who become sick are less able to explain their symptoms to medical personnel, and medical personnel are more likely to disregard their complaints and assume that they are simply part of the mental illness. There also is evidence that some persons with schizophrenia have an elevated pain threshold so they may not complain of symptoms until the disease has progressed too far to be treatable.

 

Homelessness: Although it has not been well studied to date, it appears that homelessness increases the mortality rate of individuals with schizophrenia by making them even more susceptible to accidents and diseases.

Antipsychotic Medications

Antipsychotic drugs are used in the treatment of schizophrenia. These medications help relieve the delusions, hallucinations, and thinking problems associated with this devastating disorder. Scientists believe the drugs work by correcting imbalances in the chemicals that help brain cells communicate with one another. As with drug treatments for other physical illnesses, many patients with severe mental illnesses may need to try several different antipsychotic medications before they find the one, or the combination of medications, that works best for them.

Older conventional or standard antipsychotics include: chlorpromazine (THORAZINE); fluphenazine (PROLIXIN); haloperidol (HALDOL); thiothixene (NAVANE); trifluoperazine (STELAZINE); perphenazine (TRILAFON) and thioridazine (MELLARIL).

Atypical antipsychotics are newer drugs and include: risperidone (RISPERDAL); clozapine (CLOZARIL) and olanzapine (ZYPREXA).

 

Since these medications do not work immediately, experts recommend that doctors give the antipsychotic time to take effect before switching to another antipsychotic, adjusting the dose, or adding another medication.

 

Antipsychotic drugs are usually taken daily in tablet or liquid form. Fluphenazine (PROLIXIN) and haloperidol (HALDOL), for example, also can be given in long-acting injections (called "depot formulations") at one- to four-week intervals. With depot formulations, medication is stored in the body and slowly released. This can be especially helpful for patients who have a hard time taking pills on a daily basis.

 

Adverse Effects of Antipsychotic Medication

Most common adverse effects: dry mouth, constipation, blurred vision, and drowsiness.

Less common adverse effects: decreased sexual desire, menstrual changes, and stiff muscles on one side of the neck and jaw.

More serious adverse effects: restlessness, muscle stiffness, slurred speech, tremors of the hands or feet. Agranulocytosis, a decrease in the production of white blood cells, which occurs to any significant degree only when taking clozapine, requires monitoring of the blood.

Tardive Dyskinesia is an unpleasant and serious adverse effect of antipsychotic drugs causing involuntary facial movements and sometimes jerking or twisting movements of other parts of the body. This condition usually develops in older patients, affecting 15 to 20 percent of those who have taken older antipsychotic drugs for years. In the majority of cases, the tardive dyskinesia slowly goes away when the medication is stopped.

All drugs have the potential to cause adverse reactions. Some of these are inconvenient or unpleasant, but are not serious, while others are potentially life-threatening. The true risk of various adverse drug reactions is largely unknown. The approved product labeling or "package insert" for a drug lists the percentage of patients who experienced various adverse reactions in the clinical trials conducted before the drug was approved. These percentages are a measure of the short-term risk associated with a drug in a relatively small carefully defined population of patients who are closely monitored by trained researchers.

Once a drug is approved it can be prescribed to tens of thousands of patients in the general population who may be different than the patients included in the pre-approval clinical trials. For example, they may have other medical conditions or must take other medications and the risks of adverse reactions may, or may not, be increased.

There is no requirement that adverse drug reactions be reported by health professionals after a drug is approved – reporting is voluntary. In a voluntary system, many adverse reactions are not reported. The Food and Drug Administration (FDA) has estimated that for every report of a serious reaction it receives, ten adverse events go unreported. Because we do not know the true number of adverse reactions and can only estimate the number of patients that have received a drug the risk of a particular adverse reaction cannot be estimated.