Q. Do certain drugs work best with certain depressive illnesses? What are the guidelines for choosing a drug?
here are very few kinds of depression for which there are specific antidepressant treatments. When it comes to people with Bipolar Disorder who are depressed there are some major problems. Most importantly, with any antidepressant, there is a possibility that the antidepressant treatment will cause depressed bipolar people not just to come out of their depressions, but to develop manic episodes. The possibility of an antidepressant causing mania is least when the antidepressant is bupropion (Wellbutrin). The possibility of mania is greatly reduced if depressed bipolar folks are on a mood stabilizer such as lithium, Tegretol or Depakote when they are started on an antidepressant.

Q. How do you tell when a treatment is not working? How do you know when to switch treatments?
Antidepressant treatment is clearly not working when the individual receiving the treatment remains depressed or becomes depressed again. When a recently started antidepressant fails to cause improvement, the depressed individual often asks that the medication be stopped, and a new one started. It generally does not make sense to change antidepressants until 8-weeks at the maximum tolerated dose have elapsed. With some tricyclic antidepressants, it is important to check the blood level of the antidepressant before it is stopped. The blood test can tell if the amount in the blood has been adequate. Only after an adequate trial of one antidepressant should another be tried. To have been on four antidepressants in an 8-week period means that one has not had an adequate trial on any of them.

Q. How do antidepressants relieve depression?
There are several classes of antidepressants, all of which seem to work by increasing levels of certain neurotransmitters (most commonly serotonin, norepinephrine, and dopamine) in the brain. It is not entirely clear why increasing neurotransmitter levels should reduce the severity of a depression. One theory holds that the increased concentration of neurotransmitters causes changes in the brain’s concentration of molecules, receptors, to which these transmitters bind. In some unknown way it is the changes in the receptors that are thought responsible for improvement.

Q. Are Antidepressants just “happy pills?”
No matter what their exact mode of action may be, it is clear that antidepressants arel;l not “happy pills.” There is no street-market for antidepressants; unlike “speed” which will improve the mood of almost everybody, antidepressants only improve the mood of depressed people. Also unlike the almost instant effects of speed, the mood-improving effects of antidepressants develop slowly over a number of weeks. “Speed” induces a highly artificial state, antidepressants cause the brain to slowly increase its production of naturally occurring neurotransmitters.

Q. What percentage of depressed people will respond to antidepressants?
Generally, about 2/3 of depressed people will respond to any given antidepressant. People who do not respond to the first antidepressant they have taken, have an excellent chance of responding to another.

Q. What does it feel like to respond to an antidepressant? Will I feel euphoric if my depression responds to an antidepressant?
The most common description of the effects of antidepressants is that of feeling the depression gradually lift, and for the person to feel normal again. People who have responded to antidepressants are not euphoric. They are not unfeeling automatons. The are still able to feel sad when bad things happen, and they are able to feel very happy in response to happy events. The sadness they feel with disappointments is not depression, but is the sadness anyone feels when disappointed or when having experienced a loss. Antidepressants do not bring about happiness, they just relieve depression. Happiness is not something that can be had from a pill.

Q. What are the major categories of anti-depressants?
There are many classes of antidepressants. Two kinds of antidepressants have been around for over 30 years. These are the tricyclic antidepressants and the monoamine oxidase inhibitors. While there are newer antidepressants, many with fewer side-effects, none of the newer antidepressants has been shown to be more effective than these two classes of drugs. In fact, many people who have not responded to newer antidepressants have been successfully treated with one of these classes of drugs.

The tricyclic antidepressants (TCAs) include such drugs as imipramine (Tofranil, amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Aventyl and Pamelor).

The monoamine oxidase inhibitors (MAOIs) include tranylcypromine (Parnate), phenelzine (Nardil), and isocarboxazid (Marplan) which has recently been taken off the market in the U.S.A. for marketing rather than safety or efficacy reasons.

One of the popular new classes of antidepressants are the selective serotonin reuptake inhibitors (SSRIs). The first of these drugs to be marketed in the USA was fluoxetine (Prozac). Sertraline (Zoloft), and paroxetine (Paxil) soon followed, and fluvoxamine (Luvox) is scheduled to be marketed in late 1994, or early 1995.

Bupropion (Wellbutrin) is the only drug in its class, as is trazodone (Desyrel). The most recently marketed antidepressant (4/94) is venlafaxine (Effexor), the first drug in yet another class of drugs.

Q. What are the side-effects of the commonly used antidepressants?
Below is a list of some of the more frequently prescribed antidepressants, and their most common side effects. The figure following each side effect is the percentage of people taking the medication who experience that side effect.

  • Aventyl (nortriptyline): Dry mouth (15); Constipation (15); Weakness-fatigue (10)┬áTremor (10).
  • Effexor (venlafaxine): Nausea (35); Headache (25); Sleepiness (25); Dry mouth (20); Insomnia (20); Constipation (15).
  • Elavil (amitriptyline): Dry mouth (40); Drowsiness (30); Weight gain (30); Constipation (25); Sweating (20).
  • Nardil (phenelzine): dry mouth (30); insomnia (25); Increased heart rate (25); Lowered blood pressure (20); Sedation (15); Over stimulation (10);
  • Norpramin (desipramine): dry mouth (15); increased pulse (15); constipation (10); reduced blood pressure (10).
  • Pamelor: see Aventyl
  • Parnate (tranylcypromine): Dry mouth (20); Insomnia (20); Increased pulse rate (20); Lowered blood pressure (15); Over stimulation (15); Sedation (15).
  • Paxil (paroxetine): Decreased sexual interest and/or problems achieving orgasm (30); Nausea (25); Sedation (25); Dizziness (15) Insomnia (15)
  • Prozac (fluoxetine): Decreased sexual interest and/or problems achieving orgasm (30); Nausea (20); Headache (20); Nervousness (15); Insomnia (15); Diarrhea (15).
  • Sinequan (doxepin): Dry mouth (40); Sedation (40); Weight gain (30); Lowered blood pressure (25); Constipation (25); Sweating (20).
  • Tofranil (imipramine): Dry mouth (30), Reduced blood pressure (30), Constipation (20), Difficulty with urination (15).
  • Wellbutrin (bupropion): Agitation (30); Weight loss (25), Dizziness (20); Decreased appetite (20);
  • Zoloft (sertraline): Decreased sexual interest and/or problems achieving orgasm (30);Nausea (25); Headache (20); Diarrhea (20); Insomnia 15); Dry mouth (15); Sedation (15).

Q. What are some techniques that can be used by people taking antidepressants to make side effects more tolerable?
Listed below are some frequent side effects of antidepressants, and some techniques to reduce their severity:

  • Dry mouth: Drink lots of water, chew sugarless gum, clean teeth daily, ask the dentist to suggest a fluoride rinse to prevent cavities, visit the dentist more often than usual for tooth and gum hygiene
  • Constipation: Drink at least six 8-ounce glasses of water every day, eat bran cereals, eat salads twice a day, exercise daily (walk for at least 30 minutes a day), ask your doctor about taking a bulk producing agent such as Metamucil, also ask about taking a stool softener such as Colace, be sure to avoid laxatives such as Ex-Lax.
  • Bladder problems: The effects of some antidepressants, especially the tricyclic medications may make it difficult for you to start the stream of urine. There may be some hesitation between the time you try to urinate and the time your urine starts to flow. If it takes you over 5-minutes to start the stream, call your doctor.
  • Blurred vision: The tricyclic antidepressants may make it difficult for you to read. Distant vision is usually unaffected. If reading is important to you the effects of the antidepressant can be compensated for by a change in glasses. As you may compensate for the change in your vision, try to postpone getting new glasses as long as possible.
  • Dizziness: Dizziness when getting out of bed or when standing up from a chair, or when climbing stairs may be a problem when taking tricyclic antidepressants and monoamine oxidase inhibitors. Changing posture slowly may help prevent this kind of dizziness. Drinking adequate amounts of liquid and eating enough salt each day is important. Be sure to speak to your doctor if this side-effect is severe.
  • Drowsiness: This side effect often passes as you get used to taking the antidepressant that has been prescribed for you. Ask your doctor if it is safe for you to increase your intake of caffeine, and if so, by how much. If you are drowsy be sure not to drive or operate dangerous machinery.

Q. Many antidepressants seem to have sexual side effects. Can anything be done about those side-effects?
Both lowered sexual desire and difficulties having an orgasm, in both men and women, are particularly a problem with the selective serotonin re-uptake inhibitors (Prozac, Zoloft, Paxil and Luvox), and the monoamine oxidase inhibitors (Nardil and Parnate). There is no treatment for decreased sexual interest except lowering the dose or switching to a drug that does not have sexual side effects such as bupropion (Wellbutrin). Difficulty having orgasms may be treated by a number of medications. Among those medications are: Periactin, Urecholine, and Symmetrel. None of these are over-the-counter drugs and they must be prescribed by a physician. Unfortunately, many psychiatrists are not familiar with using these medications to treat the sexual side-effects of antidepressants.

Q. What should I do if my antidepressant does not work?
Many people decide that their antidepressant is not working prematurely. When one starts an antidepressant the hope is for rapid relief from depression. What must be remembered is that for an antidepressant to work, you must be on an adequate dose of the drug for an adequate length of time. A fair trial of any antidepressant is at least two months. Prior to a two month trial the only reason to abandon an antidepressant trial is if the medication is causing severe side effects. With many antidepressants the dose has to be increased at intervals far above the starting dose. Unfortunately, the two-month period mentioned above, refers to two months following the most recent increase in the dose, not the time from starting the particular antidepressant.

Q. Can someone build up tolerance to Prozac or other anti-depressants so that they stop working after a while?
Tolerance to Prozac and the other SSRIs is a relatively rare phenomenon. What looks like tolerance may develop because the SSRIs also have effects on the dopamine systems of the brain, and these effects can slow one down dramatically.

When an SSRI sems not to be working as well as it once did, it often can be helped to work once again by adding small doses of a dopaminergic agonist such as dextrroamphetamine, Ritalin, or bromocriptene. Also, certainly with Proxzac, and possibly with other SSRIs, too much of the drug is as ineffective as too little. If raising the dose does not help, an certainly if it makes things worse, a lowering of the dose may do much to bring back a response.

I am convinced that many patients respond best is they are treated with one of the SSRIs + a tricyclic antidepressant such as desipramine (Norpramin), or nortriptyline (Aventyl). Such combinations are often effective when an SSRI by itself fails to do the job.

Q. If an antidepressant has produced a partial response, but has not fully eliminated depression, what can be done about it?
There are many techniques to help an antidepressant work more completely. The simplest is to increase the dose until relief is experienced or side- effects are severe. If the dose can not be increased, lithium can be added to any antidepressant to augment its effect. With all antidepressants it is possible to add small doses of stimulants such as pemoline (Cylert), methylphenidate (Ritalin), or dextroamphetamine (Dexedrine) to augment the antidepressant effect. Selective serotonin re-uptake inhibitors often work better when small doses of desipramine (Norpramin) or nortriptyline (Aventyl and Pamelor) are co-administered. Thyroid hormones (Synthroid or Cytomel) may be used to augment any antidepressant. At times combinations of these techniques may be utilized.