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Bad Trip by Prescription
Fluoxetine & Trazodone
by bonze
Citation:   bonze. "Bad Trip by Prescription: An Experience with Fluoxetine & Trazodone (exp91808)". Aug 28, 2018.

20 mg oral Pharms - Fluoxetine (daily)
  50 mg oral Pharms - Trazodone (daily)


My FDA MedWatch adverse event report, as submitted via their web form on 12/30/2002<-- - bonze Anne Rose Blayk _______________________________________________________________________

Kevin Eric Saunders a/k/a bonze blayk

Describe event or problem up to a total of 6400 characters allowed

NOTE... my GP is Dr. Breiman of Family Medicine Associates, 209 W. State St., Ithaca, NY 14850. The psychiatrist who prescribed the drugs which caused the adverse reactions was the (now-deceased) Dr. Robert Hamlisch. If you would please provide me with an email contact address, I can also submit research citations in RTF format which support this analysis.-->

SUMMARY: Concurrent use of fluoxetine (Prozac, 20mg/day in the morning as an antidepressant) and Trazodone (50 mg/day at bedtime as a 'sleep aid') over 6 days led to peripheral numbness, heart palpitations, urinary retention, visual distortions, and eventually paranoia and delusions. Discontinuation of Trazodone after 6 days and later substitution of Hydroxyzine Pamoate (25 mg) as a 'sleep aid' further complicated the adverse reaction, eventuating in frank psychosis with prominent auditory hallucinations (2/5/97).

Fluoxetine was initiated 12/28/96, followed by Trazodone (taken at bedtime) on 1/4/97.

On an ER visit on 1/11/97 physical symptoms listed above were dismissed by the ER examiner as effects of 'agitated depression.' (Fluoxetine had been used 8/96 - 10/96 at 10mg/day, but had been discontinued due to mildly unpleasant side effects.)

I discontinued Trazodone, since according to the Trazodone insert it might be a possible cause of the heart palpitations I had felt; on 1/16/97 Hydroxyzine Pamoate (Vistaril) was prescribed as an alternative 'sleep aid,' resulting in extreme anticholinergic side effects and worsening of paranoia.

I believed I was suffering from a serious neurological disorder, and resumed smoking cannabis for about two weeks (through 1/28/97) in the hope I would experience some relief of the symptoms. (NB: I had never experienced any significant negative side affects from smoking marijuana over 20 years of fairly regular use, which had been discontinued more than one month prior to going on fluoxetine ... nor, prior to this incident, psychosis from any cause.) Use of cannabis was discontinued in the expectation that I would soon be undergoing an NCV test for the presence of neurological problems (since use of cannabis could conceivably be reducing inflammation or affecting other neuropathic processes).

For some period during this interval, I completely lost all sensations of appetite, and lost 20 pounds.

On 2/6/97 I suffered a major psychotic episode involving delusions and auditory hallucinations.

Since the psychosis wound up resulting in serious criminal charges, consequently resulting in an acquittal under New York State law as 'Not Responsible for Reason of Mental Disease or Defect,' the cause of the psychosis was considered by a number of psychiatrists, neurologists, and psychologists. No signs of brain abnormalities were found in an MRI (5/12/97). The possibility of a neurological disorder was dismissed after subsequent 3-day sleep-deprived EEG testing showed no abnormalities (2/98). The diagnosis of Cannabis-Induced Psychotic Disorder was also considered and dismissed.

Psychiatric and psychological examiners made varying diagnoses, including some questioning the presence of psychosis during the criminal offense (particularly since I'd been consistently found to be rational in numerous examinations). No doctor or other examiner ever considered the possibility of side effects from Prozac, Trazodone, or Hydroxyzine as a factor.

Around May 2000, I finally identified the underlying cause(s) of my physical illness in January 1997 (and subsequent psychosis) when I found research which identified both Fluoxetine and Trazodone as sodium channel blockers capable of inducing paresthesias. My suspicions having been heightened, I did more research on Trazodone, and discovered that Trazodone has an anxiogenic byproduct with hallucinogenic properties: the serotinergic agonist mCPP (meta-chlorophenylpiperazine). The anxiogenic properties of mCPP are widely used in clinical research; the hallucinogenic properties have gone largely unrecognized (though note 'The subjective effects of MDMA and mCPP in moderate MDMA users', Tancer & Johanson, PMID 11714594, and reports of delirium induced by Trazodone where these effects were probably caused by mCPP, e.g., 'Trazodone-induced delirium in bulimic patients,' Damlouji & Ferguson, PMID 6584039).

Also, mCPP is a powerful anorectic agent, accounting for my loss of appetite!

Moreover, I found that research has clearly established that Fluoxetine impairs clearance of substances metabolized by the P450IID6 enzyme (and indeed there is a warning noting this effect in the Prozac monograph)... which includes mCPP, as well as Hydroxyzine. (It is not known whether I have a defective allelle at CYPIID6 causing impaired P450IID6 metabolism -- present in about 7.5% of the Caucasian population -- since I have been unable to find a doctor or lab performing dextromethorphan/dextrorphan ratio or other tests of P450IID6 functioning.)

Thus, the 'rare' CNS side effects of paranoia, delusions, and hallucinations listed in the Trazodone monograph are statistically predictable disasters: Trazodone has tranquilizing, antipsychotic properties which ordinarily mask the anxiogenic, psychotogenic properties of mCPP... but the vagaries of metabolism may result in Trazodone clearing relatively unimpaired P450IIIA4 channels while mCPP accumulates as a result of P450IID6 blockade.

CONCLUSION: I strongly believe that the labelling of Trazodone (and, likewise, of Serzone) should clearly indicate that it produces mCPP, a panic-inducing hallucinogenic byproduct, and that clearance of this byproduct may be impaired by use of other drugs or by genetic variations affecting the P450IID6 enzyme.

Exp Year: 1997ExpID: 91808
Gender: Not Specified 
Age at time of experience: 41 
Published: Aug 28, 2018Views: 3,250
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Pharms - Fluoxetine (80), Pharms - Trazodone (294) : Combinations (3), Medical Use (47), Depression (15), Post Trip Problems (8), Health Problems (27), Not Applicable (38)

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