Posted by hyperfocus on November 2, 2011, at 18:33:24
In reply to Re: Serotonin syndrome. Amitriptyline+zoloft, posted by Abaigeal on November 1, 2011, at 7:01:47
I think what you should immediately do is have your amitriptyline blood levels checked. TCA blood levels can vary wildly in people. Some people can have extraordinary high levels of amitrip in their system than others at the same dose because of reduced clearance by their bodies. This reduced clearance can just be due to an individual's metabolism or because of concurrently taking another drug that inhibits the metabolism of the amitrip. I know for sure fluoxetine inhibits CYP450 2D6, the liver enzyme responsible for metabolizing amitrip, and combining these 2 is dangerous and not recommended. According to this article, sertaline is 4th on the list of SSRIs with this liver enzyme interaction:
http://cat.inist.fr/?aModele=afficheN&cpsidt=2889071
The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine display the following rank order of in vitro potency against the cytochrome P450 (CYP) isoenzyme CYP2D6 as measured by their inhibition of sparteine and/or dextromethorphan metabolism : paroxetine > fluoxetine = norfluoxetine > sertraline ≥ fluvoxamine > venlafaxine. On this basis, paroxetine would appear to have the greatest and fluvoxamine and venlafaxine the least potential for drug interactions with CYP2D6-dependent drugs. In vivo, inhibitory potency is affected by the plasma concentration of the free (unbound) drug, a potentially important consideration since many CYP2D6-metabolised drugs exhibit nonlinear (saturable) kinetics, and by the presence of metabolites, which might accumulate and interact with the CYP system. Under steady-state conditions, paroxetine and fluoxetine are approximately clinically equipotent inhibitors of CYP2D6 in vivo (as determined through their effects on desipramine metabolism) ; sertraline, in contrast, shows lower steady-state plasma concentrations than fluoxetine and, hence, a less pronounced inhibition of CYP2D6. Of the drugs that are metabolised by CYP2D6, secondary amine tricyclic antidepressants, antipsychotics (e.g. phenothiazines and risperidone), codeine, some antiarrhythmics (e.g. flecainide) and β-blockers form the focus of clinical attention with regard to their potential interactions with the SSRIs. Coadministration of desipramine and fluoxetine (20 mg/day) at steady-state produced an 4-fold elevation in peak plasma desipramine concentrations, while the long half-life of the active metabolite norfluoxetine was responsible for a significant and long lasting ( 3 weeks) elevation of plasma desipramine concentrations after discontinuation of fluoxetine. Similarly, coadministration of desipramine with paroxetine produced an 3-fold increase in plasma desipramine concentrations. In contrast, coadministration of desipramine and sertraline (50 mg/day) for 4 weeks resulted in a considerably more modest ( 30%) elevation in plasma desipramine concentrations. Coadministration of fluoxetine (60 mg/day, as a loading dose) [equivalent to serum concentrations obtained with 20 mg/day at steady-state] with imipramine or desipramime resulted in 3- to 4-fold increases in plasma area under the curve (AUC) values for both imipramine and desipramine (illustrating a significant drug interaction potential at multiple isoenzymes). Consistent with its minimal in vitro effect on CYP2D6, fluvoxamine shows minimal in vivo pharmacokinetic interaction with desipramine, but does interact with imipramine ( 3- to 4-fold increase in AUC) through inhibition of CYP3A3/4, CYP1A2, and CYP2C19. Thus, the extent of the in vivo interaction between the SSRIs and tricyclic antidepressants mirrors to a large extent their in vitro inhibitory potencies against CYP2D6 and other isoenzyme systems, especially if one takes into account pharmacokinetic factors.The symptoms you describe could be as a result of TCA toxicity instead of or in addition to serotonin syndrome. Amitriptyline is a Alpha-1 adrenergic receptor blocker and a fast sodium channel blocker, which is bad news for your heart. Levels of amitrip that are too high put you at risk for sudden death due to cardiotoxicity. I urge you to get your amitrip blood levels checked ASAP and DON'T increase the amitrip dose. Your story sounds a bit too close to comfort to this case:
http://www.preskorn.com/columns/0211.html"The patient denied any problems with anticholinergic side effects such as dry mouth, constipation, or urinary retention. Given that fact and the inadequate response, the amitriptyline dose was increased to 250 mg/day.
After 8 days, the patient complained of generalized anxiety, a panic episode, recurrent bouts of palpitations, and headaches. The psychiatrist concluded that the depressive episode was worsening with the development of more prominent anxiety symptoms. Given this assessment and no complaints of anticholinergic side effects, the amitriptyline dose was increased to 300 mg/day and the following medications were added: propranolol, 20 mg three times a day, diazepam, 5 mg four times a day, and flurazepam, 30 mg at night.
After 2 weeks, the patient was more listless, disinterested and confused. The assessment was worsening of the depressive episode. Given this assessment and no complaints of anticholinergic side effects, the amitriptyline dose was increased to 350 mg/day. Three days later, the patient complained of intermittent chest pain and swelling of his feet. Furosemide (Lasix) was added to treat these complaints."
The patient eventually died. I had a bit of amitrip overdose this month too btw: http://www.dr-bob.org/babble/20111016/msgs/999903.html and it was pretty scary.
C-PTSD: social phobia, major depression, dissociation.
Currently: 450mg amitriptyline single dose at night.
Also: Allegra, 1000mg Vitamin C.
Slowly improving.
poster:hyperfocus
thread:1001151
URL: http://www.dr-bob.org/babble/20111027/msgs/1001529.html