Hello Dr Firdosi

Yes, I have just looked in the BNF under Medicines Complete. Urinary retention is listed as a side effect, under 'Frequency not known' (i.e. frequency of this side effect occurring not known) and urinary incontinence is listed as an uncommon side effect. On another link, this was associated with an anticholinergic action.

In the paper below, at the end of the paragraph headed 'Gabapentin', α2δ ligands are proposed for treating people with unstable bladders when the more commonly used anticholinergic/antimuscarinic medications have not been effective:

Andersson, K. E. (2009). Prospective pharmacologic therapies for the overactive bladder. Therapeutic advances in urology, 1(2), 71-83.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126054/

Best wishes

Mary 

It has been reported to cause dry mouth and urinary retention due to intrinsic anticholinergic activity

 Thank you, Mary and Prof Opler. 

I wonder if someone is on Pregabalin and Trazadone from more than 6 months and then develop retention, which one would be the likely culprit?  

Well, according to the pharmacological profile of action pregabalin has almost nothing to do with anticholinergic activity, although this adverse events is only possible (according to the Naranjo scale, only 2-3 points; Clin. Pharmacol. Ther. 1981;30: 239–45.).

On the another side trazodone has anticholinergic activity, especially in higher doses (higher than 100 mg daily) and therefore this adverse event is more connected with this drug (according to the Naranjo scale it is about 6-7 points).

See online calculator: http://farmacologiaclinica.info/scales/Naranjo_algorithm/ 

If I conclude, this adverse event is connected with trazodone and not with pregabaline. In this point of view it is very important that you know which dose has been taken. If patients is treated with 100 mg of trazodone then you add an additional dose to 150 mg and You will see if this adverse event will be more pronounced (then you have higher level of evidence). If this adverse event is not very serious you can try to discontinue trazodone and recontinue after 7 days. If You will do this and adverse event will reappear you have the strongest evidence that this adverse event is connected with trazodone.

However, if this is very serious adverse event I suggest You to discontinue trazodone treatment and stay on pregabalin. If a sedation is big problem (discontinuation of trazodone) add mirtazapine if it is possible (e.g. no diabetes, etc ...). If trazodone in higher dose was used for depression treatment then add mirtazapine in higher doses. Mirtazapine has a potencial to add an additional holinergic activity, which improves this adverse effect (via central 5-HT-3 blockage in CNS, which leads to inactivation of GABA interneurons and activation of cholinergic neurons and norepinephrine neurons).

As clinical pharmacist specialist within psychiatry I often deal with these adverse events (in this field a cooperation between clinical pharmacist and psychiatrist is the best possible option in terms of clinical outcomes). For more data please feel free to read my papers on this topic (you can download via Reseachgate).

Štuhec M. Solifenacin-induced delirium and hallucinations.

Gen Hosp Psychiatry. 2013 Nov-Dec;35(6):682.e3-4. http://www.ncbi.nlm.nih.gov/pubmed/23866158

Štuhec M. Excessive sweating induced by interaction between agomelatine and duloxetine hydrochloride: case report and review of the literature.

Wien Klin Wochenschr. 2015 Sep;127(17-18):703-6 http://www.ncbi.nlm.nih.gov/pubmed/25576334

I hope that it was helpful!

Regards,

Matej Stuhec, Pharm.D., Ph.D.

http://www.ncbi.nlm.nih.gov/pubmed/25576334

http://www.ncbi.nlm.nih.gov/pubmed/23866158

Thank you, Matej, a quite helpful answer.  The person was on Pregabalin 600mg and Trazadone 300mg from a while now with no recent dose changes except for recent travel. 

Thanks for this positive outcome!

Trazodone is a good case of a dose dependent multifunctional drug in pharmacology. Small doses only act on the most potent binding properties (smaller Ki), but higher doses act on additional receptors (higher Ki). The most potent binding property of trazodone's is via 5HT2A antagonism (for SERTs is 100 fold less potent).

Interesting, patient has been treated with 300 mg of trazodone. In small doses trazodone has an actions predominantly on H1, alpha-1 and 5HT2C (under 150 mg daily). However, this smal dose usually does not provide effective antidepressant treatment and therefore dose adjustment is necessary (e.g. 300-600 mg of trazodone daily). In higher dose its mechanism of action can be connected with M1 receptors (although binding potential is about 50 % less than for SERT). This consequently led to this adverse effect. Usually because of up/down actions of receptors, a tolerance has been seen in these cases in the long term treatment, which is good for the adverse events.

If I sum up, mirtazapine could be a good option (additional holinergic activity). You can also try with SSRI+small doses of trazodone (50-100 mg), although a use of polypharmacy is not recommended.

Yes, some of my patient´s have urinary retention, and in this cases a good idea it´s to change to gabapantin

I had a patient has done a retention but under gabapentin 

Wow-I did not know gabapentin could cause urinary retention: any thoughts re: mechanism?

In my point of view there is no appropriate pharmacological mechanism, which can understand this adverse events in case of gabapentin.

Gabapentin acts via calcium channels ( α2δ subunit of voltage-gated calcium channels in the central nervous system.). Pregabalin promotes the production of GABA and increases neural GABA levels by producing a dose dependent increase in glutamate decarboxylase (GAD). There are many GABA' interneurons in CNS. If gabapentin has a mechanism, which acts on these interneurons the main consequence will be lower level of acetylcholine (anticholinergic effect mediated by CNS). However, this mechanism is appropriate, but in the CNS GABA' interneurons are more or less heteroreceptors (via 5HT3, via 5HT2C receptors on GABA' interneurons), this adverse effect is less likely connected with gabapentin. This can be connected with mechanism of action of mirtazapine and agomelatine, which both act via GABA' interneurons in CNS and consequently adrenaline/acetylcholine (mirtazapine) and adrenaline/dopamine (agomelatine) is released.

my patient is a nurse and she was previously under duloxetine that she stopped a few days ago then when she came for follow up  i put her on 300 mg gabapentin , 2 days later she reported that she did not urinate all the day .i told her to stop the medicine

Dear Tahir,

Yes this event is connected with mechanism of action of duloxetine HCL. When you finish with duloxetine you get an extra antiadrenergic effect (pharmacodynamic action). Duloxetine is in U.S. approved for urinary incontinence treatement. I think this action is then more withdrawal effect of duloxetine than gabapentin! I would not to suggest stop with gabapentin, because this action is because duloxetine was discontinued (12 hours is half life).

Regards