Dr. Bob's Psychopharmacology Tips

Patients who lose response to antidepressants

Date: Sat, 4 Mar 1995 10:53:43 -0500 (EST)
From: Bill Boyer <wboyer@emory.edu>
Subject: Patients who lose response to an SSRI

When encountering patients who do well for the first few weeks on an SSRI (especially Prozac) but then seem to lose their response after a few weeks I have to decide whether to increase or decrease the dose. If the patient, at that point, seems to have *new* sedation or apathy I conclude the dose is too high and decrease it. If not, I increase it. Most of the time I end up increasing the dose. If the patient seems to require a dose of the SSRI which produces sedation or apathy in order to have an antidepressant effect then I consider changing the time of day of administration (usually doesn't help) or adding a stimulant.

I confess that I have not seen many patients whose depression does better on lower SSRI doses, but I have seen a bunch who get fewer side effects that way.

Date: Mon, 3 Apr 1995 05:29:28 -0700 (PDT)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Dopamine agonists for patients who lose response to an SSRI

It has been hypothesized by Don Klein and others that what looks like decreased antidepressant effectiveness is really a state of akinesia resulting from depletion of dopamine with continuing use of the SSRIs. Based on this understanding one can treat the apparent fall-off in SSRI effectiveness with DA agonists such as bupropion, amantadine, methylphenidate, dextroamphetamine, etc. I have done this on many occasions, often with excellent results.

Date: Sat, 17 Jun 1995 14:29:36 -0700 (PDT)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Dose increase for patients who lose response to antidepressants

I have often observed that patients who respond well to low doses of an antidepressant, and lose the effect after a month or so, may regain the therapeutic effect if their dose is increased to more usual doses.

This may be a manifestation of an initial placebo response followed by a pharmacological response, or possibly something related to the pharmacokinetics or pharmacodynamics of the drug.

From: snagymd@MEM.po.com (Stephen Nagy, M.D.)
Date: Wed, 7 Feb 1996 22:07:57 -0500
Subject: Switching SSRIs for dosage creep

It seemed to me that once virtually no one developed tolerance to the antidepressant effects of SSRIs. That was when all we had available was fluoxetine. Nowadays, I prescribe more of the short-acting SSRIs, and it is my impression that more than 5% to 10% of my patients develop tolerance to their meds after taking them from one to twelve months. My patients seem to improve with an incremental increase in dose; however, one increase usually predicts that they will later need a second increase as the same phenomenon occurs. When we reach the upper limit of the recommended dosage range, I switch to an alternate antidepressant, which often works -- but not always. Sometimes such a patient will creep up on their dose of the second SSRI and then return to the first one, usually with renewed effectiveness at the initial starting dose. This phemnomenon seems so common that I mention to patients that it can happen and that if it does I want them to contact me.

The data is impressionistic, but it seems to me that I see much more of this "dosage creep" (and don't you hate that terminology!) than I used to see.

From: MKomrad@aol.com
Date: Wed, 7 Feb 1996 21:32:19 -0800
Subject: Bromocriptine for SSRI poop out

I have had a very similar experience. This is now spoken about in many psychopharm conferences as "poop out." In my experience it sometimes happens as late as 3 years into an SSRI (typically Prozac, since it's been around the longest), in as many as 20% of patients.

What is to be done? There is talk among "poop out" veterans of adding bromocriptine since there is speculation that this might be a dopaminergic depletion phenomenon. People have said this helps, but I haven't used it yet myself.

Date: 8 Feb 1996 11:06:54 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: SSRI poop out

I have a lot of experience seeing people who have failed to respond to a series of antidepressants and/or are failing to respond to a medication which used to help. I have found that evaluating four factors will usually get things back on track:

1. sleep problems
2. alcohol use
3. thyroid problems and
4. subsyndromal bipolar symptoms.

Alcohol use, even in small amounts, can disrupt sleep in sensitive individuals and I usually recommend complete abstention from alcohol.

The most common problem I have found, however, is the presence of subtle, subsyndromal bipolar symptoms, current or past, which may or may not meet criteria for mania or hypomania. These patients do best with the addition of lithium or another mood stabilizer.

Date: Fri, 10 May 1996 12:46:18 +1100
From: Angelo Ferraro <s_apf1@eduserv.its.unimelb.edu.au>
Subject: Drug holidays for poop out

This wearing off phenonemon seems to be an all too frequent occurence with the new antidepressants, in particular moclobemide. Rather than increasing the dosage, a few of my colleagues down here paradoxically suggest a day or two to a week without medication, with good results! Maybe it's got something to do with enzyme induction. Although others have suggested that this wearing off merely reflects an initial placebo response, I don't think it fully explains this phenomenon.

Date: Fri, 16 May 1997 09:20:19 -0700 (PDT)
From: ferrell@cmgm.stanford.edu (James Ferrell)
Subject: Naltrexone for SSRI poop out

Lee Dante wrote, in part:

This phenomena of the SSRI "poop out" can usually be reversed by adding 25 mg of naltrexone (marketed in the US as Revia), usually on top of supper to avoid transient nausea. In anywhere from two weeks to five of once daily dosing the SSRI regains the full effect and often is perceived as working better than it did at first. I have done this in over forty cases where this has been most gratifying. At this dose of naltrexone the incidence of side effects is very low, and the improvement is sustained over a period of years. It has been the end of poop out in my practice.

Date: Sun, 18 May 1997 11:53:46 +0500
From: "Dr. Niraj Ahuja" <niraj@giasdl01.vsnl.net.in>
Subject: Naltrexone for SSRI poop out

That reminds me of a patient with opiate dependence in the post-detox phase. He was receiving 20 mg of fluoxetine for a comorbid major depression and was improving when naltrexone 50 mg/day was added. Within 4 days, he was hypomanic. On discontinuation of fluoxetine (on the presumption of a SSRI-induced hypomania), he returned to his previous baseline over a period of one week. At that time, I did not think much of a possible interaction between fluoxetine & naltrexone. Now, I begin to wonder!

From: M. Kirsten Miller, M.D., M.P.H. <KMillerx@aol.com>
Date: Sun, 5 Apr 1998 23:20:01 EDT
Subject: Mirtazapine for SSRI poop out

I've used Remeron (mirtazapine) fairly often for Paxil "poop-out".

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