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by David M. Goldstein, M.D., Director, Mood Disorders Program, Georgetown University Medical Center

Pharmacological treatment of mood disorders - Article. Article by David M Goldstein, MD Director of the Mood Disorders Program, Georgetown University Medical Center.Effective medical treatments now exist for the full range of mood disorders, from mild depression to severe manic depression. Treatment decisions are based on the severity of the symptoms as well as the type of symptomatology. There are a wide variety of treatments that are now available, but research studies consistently demonstrate that combined psychotherapy and medication treatments produce the best results. The psychotherapy treatments work by helping with the psychosocial and interpersonal adjustment of the individual, whereas the drugs help with the physical and physiologically based symptoms. Psychotherapy seems to help by improving the patient's willingness to continue with the medication treatment, also.

This review will focus on psychopharmacological treatments for depression and manic depression. Although the mode of action of the various psychotropic medications is not precisely known, it is thought that these drugs work by correcting imbalances in the brain's chemical messenger or neurotransmitter system. The brain is a highly complex organ, and it may be that the medications work to restore normal regulatory processes in the brain. These drugs are quite effective if taken for sufficient lengths of time and at proper dosages. It is common for there to be a several week delay in the onset of effectiveness of the medication, so patience and cooperation with the prescribing physician are crucial elements in treatment. A primary cause of patients' noncompliance with medication treatment is the emergence of side effects. The side effects associated with the use of these medications generally are dependent upon dosage and duration of treatment. A close cooperative and trusting relationship with the physician is important in helping the individual to navigate through the side effects, should they occur.

These medications have been carefully studied and have to pass rigorous standards by the Food and Drug Administration in order to be released into the marketplace. All available antidepressant prescription medications have been found to be safe and effective and they are not known to be addictive.

Medication choice is guided by diagnosis, so prior to the initiation of treatment, care must be taken to accurately diagnose the medical condition that best explains the presenting symptoms. Treatments for depression and manic depression often differ and this is an important distinction. Manic depressive patients treated with antidepressants alone may be at an increased risk for the development of a manic episode.

Medication Treatments for Depression

There are over thirty antidepressant medications now available in the United States to treat depression. There are three principal neurotransmitters that are involved in the development of depression, and they are serotonin, norepinephrine, and dopamine. The available anti-depressant medications differ in which of these neurotransmitters are affected. The medications also differ in which side-effects they are likely to induce. Other differences among the medications involve how they interact with other medications that an individual might be taking. The available medications for depression can be categorized in the following way:

  1. Heterocyclic antidepressants
  2. monoamine oxidase inhibitors
  3. selective serotonin reuptake inhibitors (SSRI's).

Heterocylic antidepressants: The Heterocyclic antidepressants were the mainstay of antidepressant treatment from their inception in the United States in the late 1950's until the mid 1980's. These drugs include the tricyclic antidepressants, such as Elavil, Tofranil, Pamelor, Norpramin, and Vivactil. These medications have been quite effective in improving the symptoms of depression, but their usefulness is limited by the associated side-effects. These side-effects include dry mouth, constipation, weight gain, urinary hesitancy, rapid heartbeat, and dizziness upon arising. These side-effects, although they are rarely dangerous, may be of significant magnitude to warrant stopping that medication and switching to another. A more recent member of the Heterocyclic family is a new medication named Remeron. This is a recently released antidepressant that is chemically similar to the older compounds, although it has a more favorable side-effect profile.

The monoamine oxidase inhibitor antidepressants (MAO inhibitors): The monoamine oxidase inhibitor antidepressants, or MAOI's, are a group of antidepressants that were developed in the 1950's also. Initially they were used as treatments for tuberculosis, but were discovered to have antidepressant properties among that population. These medications can be highly effective for some individuals who have what is referred to as "atypical depression". These are patients who have a dominance of fatigue, excessive need for sleep, weight gain, and rejection sensitivity. Some investigators feel that this group of patients respond preferentially to MAOI drugs. This category of medications includes drugs such as Nardil and Parnate. There is another medication called Mannerix that is a useful drug in this category but is not commercially available in the United States. Monoamine oxidase inhibitor drugs are limited by the possibility of the infrequent but at times life threatening side effect of hypertensive crisis. This is a phenomenon where, while taking the medication, the individual eats certain foodstuffs or takes certain medications that contain an amino acid known as tyramine. This results in a sudden and severe rise in blood pressure associated with a severe headache. In some instances the use of this medication can be extremely helpful, but the dietary restrictions have to be followed faithfully.

The selective serotonin reuptake inhibitors (SSRIs) The final category of antidepressant medication is known as the selective serotonin reuptake inhibitors, or SSRI drugs. The first of these agents was Prozac, which came on the market in 1987, and was followed in short order by Zoloft, Paxil, Luvox, and more recently by Effexor and Serzone. Another medication related to this group is Wellbutrin. This group of medications has been shown to be equally effective in treating depression as compared to the older Heterocyclic and MAOI medications. The advantage of these drugs is that they have fewer and more benign side effects. Generally speaking, they have fewer cardiovascular side effects and present fewer problem to the patients or the physician. They are not without side effects, however, and some patients report symptoms such as nausea, sexual inhibition, insomnia, weight gain, and daytime sedation.

Results of treatment: Approximately 60-70% of patients who present with symptoms of depression will be successfully treated by the first antidepressant that they take. The remaining 30% of individuals may be helped by trying a second, third, or even fourth medication. In certain instances, the physician may enhance the effectiveness of a particular drug by adding on other agents, such as lithium, thyroid supplementation, or a second antidepressant concurrent with the initial medication. There are difficulties that may develop with loss of efficacy of antidepressants, also. In approximately 20% of cases, individual antidepressants seem to lose their efficacy. When this happens, the physician may change medication or try one of the enhancement strategies suggested above.