Use of low dose TCA- Tricyclic antidepressant to manage sialorrhea

THANK YOU: do you prefer desmethylated TCAs like nortryptiline, or parent TCA like amitryptiline, or does it not matter?

Lew: I am sending you a relevant review article via back channel.

Thank you!

In my view (as psychiatric clinical pharmacist specialist) TCA and clozapine should not be used in combination and consequently this combination is inappropriate, because we do not have a long term studies (even short term) and we have many suggestions about this inappropriate cimbination (SmPC, Lexi(R) etc ... ). For example, both medications are high H1 blockers, which might be problem for metabolic adverse effects and use of this cimbination may lead to dangerous arrhythmias (e.g. supraventricular) and constipation and hypotension.

I would suggest use of aripiprazole with clozapine, for which combination we have even better clinical results compared with clozapine monotherapy and with aripiprazole We can deal metabolic adverse effects connected with clozapine.

Next to aripiprazole i would use Alpha-1 blockers, such as Terazosin 5 mg daily in the evening (to avoid sedation along the day).

Next to aripiprazole i suggest Butylscopolamine tablets, for example 2 tablets daily.

Finally, i should add also mirtazapine, which also acts again hypersalivation and which is also appropriate as 'add on therapy' in treatment resistant schizophrenia or even trazodone is better as TCAs.

My advice is to avoid combination of clozapine with TCAs, especially its long term use.

Regards,

Mathew

Please see link below.: 

http://www.ncbi.nlm.nih.gov/pubmed/21906915

I like the mirtazapine idea!

I have had some good results with glycopyrrolate 

Yes, It does not cross the blood–brain barrier and consequently has no to few central effects as Trospium chloride. We do not have glycopyrrolate in most European countries and Butylscopolamine is very similar. Trospium chloride is not ideal because it can produce delirium and hallucinations (effect because of croossing of BB barrier).

Yes i also think mirtazapine is much better than TCAs. No important interactions with clozapine in normal dose and minimum probability of serious adverse events (careful on weight gain). 

There are a few options we've used... Cogentin 1mg nocte, Atropine (eye) drops,hyoscine and by accident discovered when treating someone with a spastic bladder that ditropan also helped hypersalivation. 

for mild cases benign antihistamines like loratadine, cetirizine, fexofenadine have helped, diphenhydramine for moderate cases and glycopyrrolate for more severe cases. Antihistamines have been easily accepted by patients and are relatively cheap. I am leary about adding TCA due to cardiac arrhythmias potential. Especially when they go to the GP and get antibiotics like macrolides or quinolones without thinking twice....

We use Hyoscine hydrobromide 300 micrograms upto tds with variable results. Another option is Pirenzepine (selective M1, M4 antagonist) 50 mg upto tds. Worsening of constipation should be kept in mind with both treatments.

Yes, it's very commonplace and a major hurdle for many patients to go on CLOZ.

Circa 30%. Thought of as a paradoxical phenomenon given powerful anticholinergic effects of CLOZ.

It's a dose-dependant side effect, so sometimes reducing the dose might be helpful.

Mechanisms include-

1) alfa- adrenolytic effect - so using alfa-2 agonist like Catapres might be helpful

2) M4 agonist (CLOZ is M1,2,3 and 5 antagonist) - so using M4 antagonist like pirenzepine might help. This agent is not available here, so I have no experience with it.

3) Inhibition of deglutition reflex

OR a composite thereof.

Some tips I usually give to my patients

1) sugar-free gum to chew

2) put a towel on pillow 

3) lateral decubitus position while sleeping

Some Meds to try

1) Tryptizol (TCA)

2) Atropine eye drops SL

3) Combo of terazosin+ Artane

4) Clonidine as above

5) Procyclidine

6) Pirenzepine (if available)

7) Wellbutrin (bupropion)

8) add-on dogmatil (augmentation too)

I tried Botox injection every 3-6 months with some patients and found helpful and practical

Trust this might help

Thank you. 

Article Glycopyrrolate for treatment of clozapine-induced sialorrhea in adults

Recently due to shortage of Hyoscine hydrobomide also known as scoploamine (Kwells) we had to discontinue this and start few patients on Trihexyphenidyl. Patients reported even better benefit than Kwells. Again please be mindful about the increased anticholinergic burden in addition to Clozapine and monitor closely for constipation and intervene at the earliest.

Hi professor Lewis Alan Opler

According to results of two recent decades studies there are no consensus based therapeutic strategies for complete treatment of the Clozapine Induced Sialorrhea (CIS).

Multiple receptors and neurotransmitters are affected in prescription of standard therapeutic doses. Different clozapine effect on sub types of muscarinic receptors limited the efficacy of antimuscarinic agents. However controversies to achieve significant reduction of hypersalivation by using drugs such as glycopyrrolate, benztropine, alpha2 agonists, beta-adrenoreceptor blockers, diphenhydramine and other drugs is still present.

Best Regards, Seyed Reza Abtahi