In a previous blog I distinguished between different kinds of depression and indicated that there are certain kinds of depression that I would not want to treat with anti-depressants. Someone who has just been jilted can become very sad and depressed, but this reaction is a kind of exaggerated form of grief and responds primarily to psychotherapy. A major depression ( what used to be called an endogenous depression, meaning that it is not a response to external events) is marked by so-called vegetative signs: a sleep disorder, and disorder of appetite, including sexual appetite, and a diurnal variation in mood (in which the affected person feels worse in the morning and slowly somewhat better as the day wears on.) Of course, this kind of depression can overlap with a depression that is life-long or caused by some particular recent loss. A major depression of this endogenous sort should be treated with drugs with the reasonable expectation that they will work. What follows is how I treat this condition. It is only one possible drug regimen. There are thirty or forty anti-depressant drugs on the market; and the reason for this is that no one drug has been demonstrated to be significantly better than the others. Most psychiatrists choose one drug over another because of the potential side-effects, which do differ from one drug to the next (although not as much as the manufacturers suggest.) Actually, I think psychiatrists tend to use the drugs that they are most familiar with– and this seems to me to be sensible, for the most part. All of the anti-depressant drugs that are currently available take a number of weeks to work. No one knows why. The side-effects, such as they are, tend to happen more quickly.
The more closely the patient resembles the description I have given above of someone with vegetative signs, the more certain it is that that patient will respond to treatment. This usually means that the worse the patient feels, the more likely it is that he or she will respond.
Like most psychiatrists, the first drug I give is likely to be a serotinergic drug, that is, the Prozac family of drugs, which include Zoloft, Paxil, Lexapro and a number of others. If a patient has already been started on one of these drugs by a different doctor, I usually continue that drug. Otherwise I start the patient on Prozac, for a couple of reasons: the drug has been around longer than the others and is not likely to produce unexpected side-effects and , secondly, Prozac affects the metabolism of a different anti-depressant which I usually add to the Prozac after three weeks.
The majority of patients do not respond completely to Prozac after three weeks. (They may have made some response, even earlier than three weeks.) This is a very familiar situation, so familiar, that the American Psychiatric Association has published an algorithm recommending one of two strategies:
1. To raise the level of the initial drug (Prozac, usually given in a 20 mgm dose can be raised in increments to 80 mgm.) I don’t like doing this since at higher doses, side-effects become much more common, particularly, in the case of the serotinergic drugs, a difficulty reaching orgasm. (This side-effect is so common, in fact, that Prozac in high doses is a really good treatment for premature ejaculation)
2.. Adding a different drug. What is really extraordinary about this situation, is that the drugs recommended include not only different drugs of the same class, but different drugs of 5 different classes!
a. Tryciclic antidepressants (This is what I do)
b. Lithium. A salt. This is a drug usually given in higher doses to bipolar patients, but is also effective at potentiating the serotinergic drugs.
c. Anti-psychotic drugs (used usually, as you might expect, for psychotic patients;) but in lower doses, they also potentiate the anti-depressants.
d. Amphetamines. A stimulant which can be unsafe used by itself to alleviate depression (it causes ups and down) but, once again, potentiates the effects of the anti-depressants in lower doses. (This is likely to be given when the depression causes an increase in sleepiness rather than an inability to sleep.)
e Thyroid, a hormone, even in situations where the patient is not hypothyroid.
After three weeks, I add 25 mgm of Tofranil, which is among the oldest of the anti-depressants. It works on somewhat different neurotransmitters than the serotinergic drugs. Used by itself, the therapeutic doses is likely to be between 150 and 300 mgm a day, but because there is an interaction with Prozac, 25 mgm usualy works. The other serotinergic agents are likely to require a higher dose of Tofranil. The addition of Tofranil, in my experience, works overnight! Sometimes the dose required is a little more, but not infrequently even less: 10 mgm or 20 mgm. If the dose is a little too high the patient usually feels fine but is usually too sleepy. There are other drugs, like Effexor of Cymbalta that resemble the combination of Prozac and Tofranil, but using Prozac and Tofranil together seems to me to make it easier to manage the final proper dose without unnecessary side effects.
This regimen works over 95% of the time. Rarely, I have to add an anti-psychotic. Even more rarely, adding two or three additional drugs won’t work, and the patient has to be taken off everything and put on a MAO inhibitor (which has a wider spectrum of effectiveness.) MAO inhibitors are not used first, even though they are most likely to be effective, because the patient has to stay away from certain foods and medications to prevent a potentially serious reaction.
NONE OF WHAT I HAVE WRITTEN ABOVE SHOULD BE TAKEN AS A BLANKET RECOMMENDATION FOR TREATMENT. ALL OF THESE DRUGS HAVE EFFECTS WHICH COULD POTENTIALLY COMPLICATE OTHER MEDICAL PROBLEMS. FOR INSTANCE, TOFRANIL CAN WORSEN A CLOSED-ANGLE GLAUCOMA OR A PROSTATITIS.
This is the reason why psychologists and other mental health professionals cannot sensibly recommend one drug over another. It is important to know all of medicine to understand what is potentially dangerous.
Also, of course. the patient’s desires go into choosing one drug over another. (one may be more likely to cause weight gain, another more likely to cause a sexual inhibition.) By the way, when I present this alternative to patients, I am impressed by how often the men would prefer to risk gaining weight, and the women would prefer risking a sexual inhibition.)
There are a lot of other ways of using anti-depressant drugs; but I thought it might be interesting for you to know how one particular psychiatrist does it.