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Why Your Antidepressant May Not Be Working

Posted Aug 27 2009 11:38pm
Modern antidepressant medication trials are highly effective across the board, but many patients, particularly treatment-naïve individuals who are new to taking psychotropic medications, often report that their medication isn't working as well or as quickly as they had anticipated. This article covers the most common mistakes and misconceptions patients make when first taking prescription psychotropic medication for purposes of improving their mood. Once these common problems and pitfalls have been fixed or ruled out, there are indeed various options you can explore with your prescribing physician to alter the prescribed treatment regimen and get a better response.


The medicine has not been taken for a long enough period of time. This is probably the most common reason a medication doesn't seem to be working after starting taking it, and it is simply a matter of expectation: early on, it simply hasn't had enough time to work. Although in a minority of cases a person will begin feeling better within a few days (I've seen this with the dual-acting agent Effexor a number of times, especially in individuals with moderate-to-severe symptoms that are largely due to endogenous, or physical, depression), it is more standard for a person to appreciate only mild side effects initially, for as long as two or three weeks, before gradual improvements begin to be noticed. In fact, many times just as most of the side effects are beginning to disappear, the therapeutic effect begins kicking in. It is definitely worth sticking it out until this occurs!

Even in those individuals who begin to feel better right away, the full effect of an antidepressant medication can easily take 2-4 weeks or longer to manifest. Considering that many times a starting dose will have to be optimized by increasing it a few times, depending in part on how the person is tolerating and adapting to the side effects, it could be 6-12 weeks or longer before just the right dose has been taken for long enough for a medication's full benefit to become apparent. So patience is key. That said, in the vast majority of cases, you should begin to see noticeable improvement in your symptoms well within the first month.

What can you do in the meantime? One thing your doctor can do is to prescribe other, short-term medications designed to address certain target symptoms while you are waiting to feel better. For example, if insomnia is a prominent symptom of your depression, your doctor can prescribe a short course of a sleeping medication that will treat that symptom immediately and let you get some rest while you both wait for your mood to improve. Once your depression is better, your insomnia should self-correct and you can hold the sleeping pill. Or, for example, if you are taking an "antidepressant" SSRI medication (such as Prozac, Zoloft or Lexapro) that is actually being prescribed to you to treat the symptoms of panic disorder, rather than allowing you to continue to experience panic attacks while you wait for the SSRI to take effect, panic can be very effectively blocked in the short term with what we used to call "minor tranquilizers" (such as Valium or Klonopin) while you wait the several weeks for the SSRI to begin working.

It is important, however, not to get too attached to these temporary quick fixes, because in the long run you will be much better off with the standard daily dose of the non-addictive medication that is best indicated for your condition, rather than taking pills on an as-needed basis, pills that work quickly, but typically not for long, and which are usually habit-forming. In fact, sometimes the early quick fixes actually sabotage the treatment plan (especially in individuals who are prone to substance abuse), so be sure to have an open and frank discussion with your physician if you begin to lose faith in the actual recommended treatment with its early side effects and modest, gradual gains, in favor of the sedatives and tranquilizers, and especially if you feel you are at risk of becoming addicted to those early band-aids. Overreliance on them may leave you quite disenchanted with the gold standard treatment, which works by a completely different (and ultimately, superior) mechanism and which can't compete with the "feel-good drugs."

The medication is not being taken properly and/or consistently. That is, doses are being missed. This is easy enough to do, especially if your regimen requires you to dose more than once a day, or with complicated regimens that require starting at a low dose and then titrating (adjusting) the dosage on your own, before you see the doctor again. If you are not used to taking medication you can simply forget to take it, or if the titration schedule is complicated you can become confused as to how and when to increase your dosage.

As far as effectiveness, it really doesn't matter what time of the day you take your antidepressant, and you don't even have to take it at the same time every day, but you do need to take the full dose every day. Sporadic use will diminish the benefits or even prevent any benefit, and with some medications and with regard to certain symptoms (such as anxiety and irritability), erratic dosing can actually lead to rebound symptoms in which you do worse.

Get a MedMinder or other medication dispenser; you can find them at any pharmacy and most grocery stores. They are basically medication trays consisting of a row of boxes labeled with the days of the week and sometimes with the corresponding times of the day, so that if you can't remember whether or not you've taken your medication for that day all you have to do is look.

With regard to medication regimens that change over time and that you need to ramp up or down between doctor's visits, make sure you ask your doctor to write down the dose-adjusting schedule in complete detail, especially if you are given free samples. When in doubt, call the prescriber's office and ask for clarification. Too much medication can lead to terrible side effects and too little wastes time.

The dosage is too low. For a variety of reasons, sometimes a patient will languish at a dose that is subtherapeutic, and whether it is the doctor's fault for not increasing the dosage when necessary or whether the patient doesn't return for his or her follow-up appointments in a timely manner, many people derive little or no benefit despite compliance with their treatment regimen because they are simply not taking enough. Sometimes an individual will do very well on a starting dose and months later, when s/he is feeling symptomatic again, not realize that the medication has stopped helping and that a dose adjustment is even possible. Be mindful of medication "poop-out." This is seen with Prozac and other SSRIs. A simple and modest dosage adjustment is typically sufficient to regain a positive response, and this doesn't mean that the medication will have to be increased in this manner indefinitely.

You are taking the wrong medication. When a medication stops working, sometimes a dosage change is sufficient, but other times a complete medication switch is in order. For reasons that are not understood, some medications just don't work as well for some people as they do for others; the choice of medication is often one of trial and error at the beginning.

To minimize the number of adverse trials, in choosing a medication for you your doctor will take into consideration the specific symptoms that are causing you problems, the potential for a given medication to cause unwanted side effects (certain patients may tolerate one potential side effect better than another), and your own prior medical history and family history. Family history is often helpful in determining how likely you are to benefit from treatment with a particular medication or class of medications in that, if you have a first-degree relative, such as a parent, sibling or child, who responded well to a certain medication, then starting with that medication may be a better approach than starting arbitrarily.

Your prescribing doctor can also consider augmentation strategies (combination treatments), and if you are still not responding, your primary care doctor may refer you to a psychiatrist for advanced psychopharmacologic intervention.


Untreated substance abuse is interfering with treatment. Abuse of alcohol and other recreational drugs will certainly sabotage treatment. Often patients are not completely honest with their healthcare provider, especially if they are new. Perhaps they feel embarrassed or ashamed, or maybe they are in denial or are not yet ready to give up their substance use. If you truly do not have a drinking problem, then removing alcohol from your diet should be no problem; you can always resume "social drinking" later, when your mood is all better. On the other hand, if you find it a challenge to forego drinking even for a few months, then you should seriously ask whether you are being completely honest with yourself.

Even if you do not believe that you suffer from chemical dependency, if you are having mood problems and the physical problems that go along with it (sleep disturbance, appetite and energy problems, difficulty concentrating, etc.) then taking a break from any and all other mood-altering substances before embarking upon a psychotropic medication trial almost goes without saying. In some cases just laying off the recreational drugs for a few days or a couple of weeks resolves the depressive symptoms (substance-induced mood disorders).

Even moderate use of alcohol can confound your new medication trial. Besides, if you are tired all the time and not sleeping well and you are irritable and your mind is full of negative and depressing thoughts, alcohol is contraindicated whether or not you choose to submit to a medication trial. And if you think that, "Alcohol is the only thing that makes me feel better!" then you really have something to discuss with your physician.

Psychological factors are overruling biological factors. Sometimes medications don't "work" because the problem is not primarily a physical one, even though you may be experiencing plenty of physical symptoms (e.g., because you are not sleeping well or eating right or stress is giving you headaches or indigestion, etc.). If your central nervous system is functioning within normal limits and your unhappiness has more to do with your environment, medications may not make much of a difference if you do not also address the specific stressors in your life. That includes personal relationships and work or school responsibilities.

That said, the SSRIs (Prozac, Zoloft, Lexapro, etc.) and other modern antidepressants can go a long way to block stress reactions, such as crying spells, feeling overwhelmed, angry outbursts, obsessing about your problems, dwelling on the past, worrying about the future, etc., and so even in situations which have more to do with difficult life circumstances than with unhealthy brain chemistry, a brief trial of medication can help--especially since severe stress induces psychosomatic changes, including in the nervous system, that can lead to self-sustaining illness, until the line between what is externally caused and what is internally caused becomes blurred and irrelevant.

If you do choose to see a psychiatrist the aim is for medication to reduce specific symptoms--target symptoms--enough to help you better cope with the situation in the short term and make necessary changes in the long term, but make sure you and your doctor have clearly set out what those target symptoms are and don't forget to involve your support system and consider counseling and other professional services, as appropriate. This way you will only leave the target symptoms to the medication and you will not neglect to address everything else that needs to be addressed, non-medicinally, to come out of your depression and anxiety. Some target symptoms will be completely addressed by medication, while others will improve with medication, allowing you to continue working on them with cognitive and behavioral strategies, including lifestyle choices and psychotherapy.

If dissatisfaction is significant enough, medication by itself obviously won't solve the problems at hand, and by adopting this holistic approach you will be less likely to be disappointed that the medication isn't helping if psychological factors outweigh physiological factors.


Other medications or medical conditions are interfering. Finally, very infrequently, there may be other physical reasons why you are not responding to antidepressant treatment the way you should be, but these reasons tend to be limited to certain physical aspects of your condition: sleep patterns, pain thresholds, energy level, appetite, for example, and not necessarily to more mental, global processes such as overall outlook, ability to cope, etc. And rarely if ever will a condition such as anemia, which will certainly make you feel tired, completely block any noticeable benefit from a medication designed to improve your mood. One notable, and not uncommon, exception would be hypothyroidism. Endocrine (hormonal) problems in general can have profound mood-altering effects and should be ruled out in patients in whom they are suspected. Check with your doctor.
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