Sunday, August 3, 2008

What to expect from an antidepressant

Here is what to expect and to watch for when starting an antidepressant:

1) some people will have an immediate positive effect from an antidepressant, they will notice improvement in mood or anxiety right away.

2) most people, though, will notice very gradual improvement, and it will require at least two weeks at a full dose to have a substantial change in symptoms. Some people may require a longer period of time, up to 2 or 3 months or longer, to notice a benefit.

3) many people have their worst side-effect problems in the first 1-2 weeks of starting an antidepressant. Side effects might include sleep problems, nausea, sweating, or increased anxiety (there can be many more side-effects too). Usually these side effects settle down after 1-2 weeks.
To reduce the likelihood of this being a problem, I usually start most people on a tiny dose of an antidepressant (for example, 1/4 tablet daily), to allow people to adjust more gradually. The advantage of this is less side-effects, but the disadvantage is that it could take longer to experience a benefit. Studies show that the most significant and consistent positive effects of antidepressants begin at a full daily dose (usually one tablet daily of most antidepressants).

4) Some people may have severe side-effect problems. If this happens, I usually recommend that they discontinue the medication, so that we can make a new plan. People who have bipolar disorder, or who may have a higher risk (e.g. through family history) of developing bipolar disorder, have a higher risk of severe side-effects from antidepressants, and have a higher risk of experiencing a manic episode as a result of taking an antidepressant.

5) In all cases, I like to see and hear from people frequently whenever a new medication is started, so that any possible problems can be addressed early. Sometimes side-effects can quietly pass, other times it might be best to back off, stop the medication, and try something else.

6) The benefits of antidepressants can sometimes be subjectively obvious, other times they may be quite subtle. Others around you may notice beneficial effects before you do yourself. It may be only after a few months that you can look back and see (and feel) that things are better.

7) There is evidence that antidepressants reduce the risk of relapse in recurrent depression (probably about a 50% reduction). For some people, even if they may not need the antidepressant to treat current, acute symptoms, they may benefit from continuing the medication so as to prevent relapse. Of note, studies also show that psychotherapy (CBT in particular) reduces relapse rate by about 50% as well in recurrent depression. And there is evidence that the combination of medication + psychotherapy is synergistic, and may reduce the relapse rate by 75%. Reference:

8) Sometimes you need to try several (or many) different antidepressants, before finding the one that suits you best. Different medications in the same class (e.g. the various different SSRI's) can sometimes "suit" people quite differently. For many of my patients, a combination of two antidepressants, or sometimes more complex combinations of other medications, ends up helping best. In these situations, I do think it is important to give each medication trial a good, thorough try (usually at least two months) before making major changes.


Anonymous said...

Most of the time the entire prospect of having to commit to some kind of medication trial-- or a series of medication trials, possibly lasting many months-- is so completely overwhelming that I have problems trying to initiate any kind of medication treatment. I know that many people who begin antidepressants discontinue them-- and that compliance is often poor-- but it seems to me that there is not much discussion about the difficulty in recruiting enough mental energy to commit to some kind of medication treatment that may or may not work--and that may do more harm than good, possibly due to side effects, but also possibly because some "depressive"or "anxious" symptoms are actually beneficial in some way.

In my experience, the ambivalence and anxiety associated with beginning this kind of treatment can be so intense-- and I feel that I have very little mental energy to spare, and I need that energy to make sure that I can fulfill my daily responsibilities, maintain my daily routine, etc-- that it seems almost impossible to imagine initiating this. This is so even though I can at the same time I can feel desperate for some kind of relief-- or I can recognize that the current situation is completely untenable, that I'm stuck, that I need to do something, etc-- it just seems impossible to commit to any kind of treatment trial, especially when it is unclear that there will be any kind of benefit.

I understand that "hopelessness" is perhaps considered a symptom of depression, but often this does seem pretty hopeless and overwhelming. It just seems like a bind to me: The understanding that I am in a very bad place, the recognition that I can't continue like this indefinitely, the feeling that it is almost impossible to continue this for months and years, the feeling that everything just seems focused on getting by and maintaining very basic things, feeling TIRED and overwhelmed, etc etc etc etc...yet there does not seem like there can be any kind of relief, and any kind of "treatment" seems like a kind of pacifying gesture--it just seems futile-- and it is difficult to commit to something that seems futile. It feels so overwhelming, and I can't see how any kind of medication can resolve any of this, and it doesn't even seem that an "attempt" to treat this is helpful, because it seems impossible to generate the interest or mental energy to sustain any kind of treatment attempt. (especially when it is unclear what exactly will improve...)

Which also brings me to 2 more issues that I do not often see addressed, but which seem kind of relevant: 1) I often find it very difficult to think of any of this in terms of "symptoms", and I can't relate to many "symptoms" that antidepressants target. The "symptoms" that I identify with are more along the lines of feeling completely overwhelmed, mentally fatigued, burnt out, etc. It just seems really vague, and this makes it difficult to quantify "improvement". It seems easier to commit to an antidepressant regimen if there are quantifiable changes that can occur (e.g., improved sleep or appetite). 2) If certain psychiatric disorders/symptoms are longstanding, for many years, without much relief, and have been in place throughout your teens, 20s, etc, at some point it seems to me that there are so many environmental problems standing in the way of any kind of "wellness"that it seems almost impossible for any kind of medication to help! I guess it seems that so many of the thoughts that perhaps in other situations would be considered symptomatic and untrue really ARE true. I mean: So much energy has been spent to just keep things together that you have burned many bridges, and you have little to show for your effort. (numerous aborted attempts at schooling-- some of which have left messy transcripts behind!, many jobs that have ended badly, few relationships, a poor economic situation, etc). It seems hopeless most of the time because this does seem like an accurate assessment of the situation!

I'm sorry for this long post!, I just wonder if perhaps in a future post you can address some of these issues. It seems to me sometimes that a lot of the discussion about depression and its treatments can be very alienating and can actually make me feel worse-- less hopeful-- because it does not seem to reflect my experience. I know that there is no "magic bullet" when it comes to treating depression, but sometimes it seems that the focus is always on just plugging away at different medication strategies, that "something" will likely end up helping (or perhaps not, but it's worth a committed try, etc), ...which just seems more overwhelming, and not particularly reassuring!

GK said...

I will write a separate post to try to initiate a discussion about some of the very important issues that you raise in your comment.


Anonymous said...


"There is evidence that antidepressants reduce the risk of relapse in recurrent depression (probably about a 50% reduction). "

Do you have links to studies that support this in which the whole text is accessible to folks like me who are not medical professionals?

As one who is successfully tapering off of a 4 med cocktail ( I am down to 1 med), I feel many psychiatrists confuse withdrawal symptoms with a relapse. They advocate a way too fast tapering schedule that causes people not to be successful in coming off their meds.

Anyway, I think that is what is going on with these statistics and that is why I would love to see the studies.

"For some people, even if they may not need the antidepressant to treat current, acute symptoms, they may benefit from continuing the medication so as to prevent relapse. "

I couldn't disagree more. Staying on these drugs long term caused a hearing loss and cognitive issues. Not exactly conducive to preventing depression relapses even though I refuse to let myself go down that path.

By tapering slowly, I have been able to avoid a relapse in spite of dealing with a family member's death and job woes. Many people have similar stories.

But in my opinion, psychiatrists don't want to hear about success stories like ours. I am not saying you're doing that by the way but it sounds like you really need to rethink your position about people needing to stay on meds for life.

"Of note, studies also show that psychotherapy (CBT in particular) reduces relapse rate by about 50% as well in recurrent depression. And there is evidence that the combination of medication + psychotherapy is synergistic, and may reduce the relapse rate by 75%."

The studies I have seen show that initially, the combination of medication and psychotherapy works the best. But the further you go out, psychotherapy works almost as well as the combo routine.

Thank for letting me post my opinion.


GK said...

Thank you for your comment.

I have helped many people taper successfully off of antidepressants and other psychiatric medications. And I strongly believe in the principle of slow tapering. Many antidepressants come in tablet sizes that make it hard to taper gradually (see my post on discontinuing antidepressants). I advocate 10% dose reductions every 1-2 weeks for people who have been on meds for long periods of time, and who wish to taper without the confounding effects of withdrawal.

Having said this, I also recognize that there are many people whose depression has been successfully treated with medication, long-term. Slow, gentle attempts at dose reduction have not helped. Many people I have seen struggling with depression have been very reluctant to consider medications, for a variety of reasons, and have engaged in vigorous, long-term courses of psychotherapy, alternative medicine, positive lifestyle change, etc. (I strongly affirm most of these efforts--with the exception of some types of alternative medicine--and would encourage them in everyone, medications or not).

The medication issue is a sensitive one, because for many people, they don't work very well, or the burden of side effects outweighs any benefit. And many people are prescribed medications without any discussion of other healthy changes and psychotherapy that are immensely important, and which reduce any need for medication treatments.

But for many others, medications have helped substantially to improve quality of life, and this benefit has, for them, required long-term medications treatment.

Individuals have a tendency to generalize their own experience, and to therefore advise other people based on this. If it is a glowingly positive experience (e.g. with yoga, CBT, meditation, or with antidepressants), they will tend to encourage others to do this. If an individual has a bad experience (e.g. with side effects, lack of benefit, or even a worsened mood state), that person may tend to strongly discourage others from considering this same path, and may also strengthen their opinion by finding a community of others with similar experiences. This is very understandable, and is human nature. Also it could lead to valuable insights about potential risks of existing therapies.

However, such phenomena cannot be the sole standard which guides care. We need to have careful research which backs up treatment decisions. Otherwise, for example, every person who has a bad experience of penicillin, heart surgery, insulin treatment for diabetes, stem cell transplant for lymphoma, vaccination against measles, or appendectomy might have excessive power to discourage others in need of such potentially life-saving therapies, based on their own individual negative experience.

I will quote some studies for you in a future post to back up my claim that antidepressants reduce relapse rates for the majority of people with recurrent depression. My evidence also comes from my own clinical experience, despite my own practice of not pushing the idea of medications, encouraging careful trials of medication discontinuation, always offering psychotherapy in various styles (long-term if necessary), and always strongly emphasizing healthy lifestyle change.

Anonymous said...

Neat information published in Nature Drug Reviews this month.

Nature Reviews Drug Discovery 7, 426-437 (May 2008) | doi:10.1038/nrd2462

Title: Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders

Authors: Gerard Sanacora1, Carlos A. Zarate, John H. Krystal1 & Husseini K. Manji

Oh and...This updating news on drug development.

Title: Deal watch: NR2B antagonist pursued for treatment-resistant depression