Let’s review the current medications in common use for treatment of depression. I am not a physician; I can’t say anything about dosing instructions, and I can only give general guidelines about what kinds of meds are appropriate for what kinds of conditions. I have little to say about how they work, because no one really knows much about that; the original explanation, that SSRIs work by stabilizing serotonin levels in the brain, seems doubtful now, but no one has come up with another explanation.
There are always new medications in the pipeline and new research findings about current medications, so it’s difficult to keep current. In what follows I’m relying heavily on two websites that try to keep up to date, John Grohol’s Psych Central and John McManamy’s McMan’s Depression and Bipolar Web. McManamy, a bipolar survivor, deserves special credit for keeping his site running on donations and subscriptions, and avoiding Big Pharma advertising. Another reliable resource is Gorman’s Essential Guide to Psychiatric Drugs.
Medications for depression fall into several major groups: MAOI inhibitors, tricyclics, SSRIs and SNRIs, and a few others that are hard to classify. There are also the mood stabilizers that are used for bipolar disorder, ADHD drugs, stimulants like amphetamines, and anti-anxiety medications.
This term refers to drugs that inhibit monoamine oxidase, a naturally occurring chemical in the brain. The usual drugs in this class in the U.S. are Marplan, Parnate, and Nardil. In Europe, these were (pre-SSRI) usually considered the first line of treatment, preferred over tricyclics, while in the U.S. they are often resorted to only when everything else has failed. They have some unpleasant side effects, but their main disadvantage is that they may cause a fatal stroke or dramatic increase in blood pressure if certain foods containing the compound tyramine are consumed (cheese, red wine, pickles, among others). However, they are so effective with a small group of people that the relief they provide far outweighs the disadvantages. In my limited experience, when MAOIs work they seem to make people a little hyper and obsessional—people will get an idea and follow it far beyond where others would have given up—but they are energized and do feel much better.
Until the advent of SSRIs, tricyclics were the standard treatment for depression. These medications include imipramine (Tofranil), amitriptiline (Elavil), nortriptyline (Vivactil, Pamelor), desipramine (Norpramin), and doxepin (Sinequan). These are all related to antihistamines, and in fact if you take Benadryl with one of these you may really dry up. They were derived from the serendipitous finding that tubercular patients treated with antihistaminic compounds sometimes became unexplainably cheerful. New research has shown that they have about the same success rate as SSRIs, with 40 to 60 percent of patients showing signs of improvement within the first three months. Since they all are available generically, their cost can be minimal. But although they can be quite effective medications, there are several drawbacks to their use. They usually take several weeks of faithful administration to be effective, which is difficult to tolerate when patients are feeling in real distress. Side effects include urinary retention, sun sensitivity, dry mouth, weight gain, and constipation. Most important, it is relatively easy to take a fatal overdose—a few weeks' supply—so psychiatrists are in a difficult position with acutely depressed patients who may benefit from tricyclics long term but may be given a means to self-destruction in the short term. Because tricyclics require a certain level in the bloodstream to be effective, it doesn't do any good to take one when feeling blue. Some tricyclics are rather sedating, which is a disadvantage for most people, but they can be used at bedtime for patients with difficulty sleeping. They are not addictive and you don’t get a buzz with them, so they’re not a drug of abuse. They must be used with care with patients who have cardiovascular disease.
Considering how vastly more popular they are, it’s amazing that SSRIs actually have so many of the drawbacks I just listed for TCAs, plus more. Such is the power of pharmaceutical marketing. Like TCAs, you need to take these drugs for several weeks to feel an effect, and you have to take them faithfully; generally, you won’t feel any better just by popping one or two (but some people feel something is happening right away). Some SSRIs are sedating for some people, while others find them energizing; in fact, people have a lot of idiosyncratic reactions to them. You may get terribly anxious, not be able to sleep, and have acute digestive problems from one SSRI, but be perfectly fine with a closely related drug.
SSRIs are not particularly lethal if you overdose on them; that alone may account for why so many physicians prefer prescribing SSRIs. They are generally touted to have fewer side effects and to be more easily tolerated than tricyclics, but that impression is a holdover from the early years when we didn’t know about the very common weight gain and loss of sexual interest and performance associated with their use. Almost every man I’ve known taking an SSRI has had to turn to Viagra or something like it; but that doesn’t do anything for the subtle loss of interest in sex that affects both men and women. For many patients these side effects alone are deal breakers. As for SSRIs being more easily tolerated, in most studies, whether it’s a TCA or an SSRI, the majority of patients stop treatment within three months. The conclusion is that SSRIs are generally no more effective than TCAs, and now we know that withdrawal from them can be very difficult.
Nevertheless, these are often effective drugs for the truly depressed, and probably what your doctor will first prescribe. The theory behind them is that there are two chemicals, serotonin and norepinephrine, that have to do with the transmission of impulses between nerve cells in the brain and seem to be associated with depression. It seems as if depressed people burn up these chemicals more quickly than other people. SSRIs were thought to help to maintain serotonin at more stable levels in the synapses, apparently leading to feelings of reduced anxiety, more security, and increased self-worth, assertiveness and resilience. SNRIs are supposed to do the same for serotonin but also affect norepinephrine. Unfortunately, no one has been able to confirm that this is actually the way these drugs work.
Then there are serotonin-norepinephrine reuptake inhibitors (SNRIs):
Some of these drugs have their own reputations in the field, some of it based on science, some not. Cymbalta is marketed to help with the physical pain that accompanies depression. Prozac is thought to be more energizing, Paxil more calming. Paxil is reputed to be the most likely to cause difficult withdrawal problems, and is known to trigger manic episodes among undiagnosed bipolar patients. Lexapro is supposed to be easily tolerated. Pristiq is just extending Effexor’s patent.
These drugs, in my opinion, should never be used by children, except under the most extreme circumstances. When children are in emotional distress, it’s usually got something to do with what’s going on at home, and there are family therapists out there who are good at helping you fix whatever the problem is. We also have no idea about the long-term effect of SSRIs on the developing brain. We have become far too quick to medicate children, putting them in chemical handcuffs when they don’t behave.
They also must be used with extreme caution with adolescents. It’s still controversial whether or not they make some teens more likely to commit suicide, but the same caution applies: we don’t know what SSRIs can do to a developing mind. Most of the teens I’ve worked with, and the adults whose depressions began in their teens, have fairly straightforward reasons for being depressed; they don’t feel loved at home, they don’t fit in at school, they’re being abused, bullied, or discriminated against, home is chaotic and they feel responsible. Giving kids like this an SSRI with no attempt at counseling is an insult; it’s telling them to shut up and go away. It is true that there are a few teens who develop depression (or a related condition like anorexia or school phobia) seemingly out of the blue, and again we don’t want to let depression rob them of years when they need to be learning how to do things, so sometimes antidepressants can be helpful. There are also young people whose depression may have been started in response to their life situation, but the depression has taken on a life of its own and the symptoms are so debilitating that meds should be considered. It’s important that the teen buy into this treatment, as part of a plan that includes psychotherapy, coming from loving parents who don’t want him to suffer unnecessarily.
(from Undoing Depression: What Therapy Doesn’t Teach You and Medication Can’t Give You. Second edition © 2010, Little, Brown & Co. All facts asserted herein are documented in the book.)