Well, there are antipsychotics like reserpine and clozapine, which we can rule out immediately. There's isoproterenol, a β-adrenergic agonist, which would probably trash your sleep via, well, mimicking epinephrine. Looks like the drugs with the fewest side effects are pilocarpine and cevimeline. If you can tolerate some sweating and/or increased urination and/or nausea, one of these might be the way to go.
Am J Psychiatry 162:1023, May 2005© 2005 American Psychiatric Association
Pilocarpine Treatment of Xerostomia Induced by Psychoactive Medications
Kim J. Masters, MD St. Simons Island, Ga.
TO THE EDITOR: Dry mouth (xerostomia) is a frequent complication of psychoactive medications with antimuscarinic and anticholinergic side effects. The lack of saliva is annoying to patients, impairs their ability to masticate and digest food, and is a potential source of dental morbidity, including increased risk for caries and oral infection. Pilocarpine is a cholinergic muscarinic agonist. It has been used to treat xerostomia induced in cancer patients by head and neck radiotherapy (1). It has recently been found to be effective in doses of 20 mg/day in a randomized, placebo-controlled dose-adjustment study in the treatment of dry mouth and dry eyes in patients with Sjogren's syndrome (2). It has been used to treat dry mouth as a complication of opioid treatment (3). Toxicity has been infrequently reported (4). However, it is contraindicated in patients with angle-closure glaucoma.
We have empirically used pilocarpine in doses of 10–30 mg/day, divided into dosing of two or three times a day. We have used it with our acute psychiatric inpatients, ages 20–69, who complained of dry mouth after they had been started on psychoactive medication. These included atypical antipsychotic agents, particularly clozapine and olanzapine; anticholinergic agents, primarily benztropine; and antidepressants, particularly tricyclic antidepressants and mirtazapine. Substantial relief of dry mouth was achieved in most patients. Side effects were mainly sweating and increased urination. We did not observe any adverse impact on psychiatric symptoms. The patients were generally pleased that their dry mouth symptoms responded rapidly, usually within 1 day, to pilocarpine treatment. Further investigation into the use of pilocarpine for the treatment of xerostomia induced by psychoactive medication seems warranted.
• For head and neck cancer patients with symptomatic xerostomia following radiation therapy using conventional fractionation schedules, pilocarpine at 5 mg three times per day is recommended.
• Patients must have evidence of preexisting salivary function and no medical contraindications to pilocarpine therapy.
• The ideal duration of treatment with pilocarpine is undefined. The decision to extend treatment beyond three months can be based only on clinical judgment and not on evidence.
• It is reasonable to use pilocarpine for patients with symptomatic xerostomia following hyperfractionated or accelerated fractionation radiotherapy.
A comparison of artificial saliva and pilocarpine in the management of xerostomia in patients with advanced cancer
Andrew N Davies Palliative Medicine, St Christopher's Hospice, London
Charles Daniels, Rosamund Pugh; Palliative Medicine, Forest Holme, Poole
Kiran Sharma; Palliative Medicine, St Catherine's Hospice, Crawley
This was a crossover study comparing a mucin-based artificial saliva (Saliva OrthanaTM) and pilocarpine hydrochloride (SalagenTM) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.
Key Words: saliva, artificial • pilocarpine • xerostomia • neoplasms • palliative care
Palliative Medicine, Vol. 12, No. 2, 105-111 (1998)
Oral Pilocarpine for Post-Irradiation Xerostomia in Patients with Head and Neck Cancer
Jonas T. Johnson, Gerald A. Ferretti, W. James Nethery, Ingrid H. Valdez, Philip C. Fox, David Ng, Charles C. Muscoplat, and Susan C. Gallagher
Background and Methods We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks.
Results We studied 207 patients who had each received 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine.
Conclusions Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating.
However, beware if you're Japanese or skinny!
Volume 36, Issue 3, Pages 310-313 (June 2009)
Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese
Naoki Nakamuraa, Nakashi Sasanoa, Hideomi Yamashitaa, Hiroshi Igakia, Kenshiro Shiraishia, Atsuro Teraharaa, Takahiro Asakageb, Kazunari Nakaob, Yasuhiro Ebiharab, Kuni Ohtomoa, Keiichi Nakagawaa
Received 23 December 2007; accepted 14 April 2008.
Objective: To evaluate Japanese tolerability to pilocarpine of 5mg t.i.d.
Methods: From January 2006 to July 2006, 39 patients with xerostomia received 5mg t.i.d. pilocarpine for at least for 12 weeks unless they had experienced unacceptable adverse effects. All patients received radiotherapy that included the parotid glands in the radiation field >50Gy. The body weights of the patients ranged from 42 to 73kg (median 60kg).
Results: Thirty-six of the 39 patients were evaluable. The tolerated rate was only 47%. Of the 25 patients whose body weights were less than 65kg, the tolerated rate was 36%, whereas the rate of the 11 patients whose body weights were 65kg or above was 72% (p=0.050). The most common adverse effect was sweating with an incidence of 64%. Response rate, which was defined as the total number of patients with an increase of at least 25mm from the baseline in the VAS score divided by the number of maintaining patients among those who started pilocarpine after more than 4 months from the start of radiotherapy, was 40% at 12 weeks (n=15).
Conclusion: For Japanese, 5mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse effects. A lower dose of pilocarpine needs to be considered.
Keywords: Pilocarpine, Xerostomia, Japanese, Tolerability, Sweating, Radiotherapy
Cevimeline for the Treatment of Xerostomia in Patients With Sjögren Syndrome
A Randomized Trial
Rose S. Fife, MD; Walter F. Chase, MD; Robin K. Dore, MD; Craig W. Wiesenhutter, MD; Peter B. Lockhart, DDS; Elizabeth Tindall, MD; James Y. Suen, MD
Arch Intern Med. 2002;162:1293-1300.
Background Cevimeline hydrochloride is a cholinergic agent with muscarinic agonist activity prominently affecting the M1 and M3 receptors prevalent in exocrine glands. We evaluated the safety and efficacy of cevimeline in the treatment of xerostomia in patients with Sjögren syndrome.
Methods Seventy-five patients with Sjögren syndrome and associated salivary gland dysfunction were enrolled in a double-blind, randomized, placebo-controlled trial at 8 university- and office-based outpatient clinical facilities in the United States. Eligible study participants were randomized to receive 30 mg of cevimeline 3 times daily, 60 mg of cevimeline 3 times daily, or placebo for 6 weeks. Subjective responses were determined using global patient evaluation and visual analog scales. Salivary flow was measured objectively.
Results Sixty-one participants completed the study. Patients in both cevimeline groups had significant improvements in dry mouth, as indicated by symptoms, salivary flow, and use of artificial saliva, compared with the placebo group. The drug was generally well tolerated, with expected adverse events resulting from the drug's muscarinic agonist action. Fourteen patients withdrew from the study because of adverse events, the most frequent being nausea.
Conclusions Therapy with cevimeline, 30 mg 3 times daily, seems to be well tolerated and to provide substantive relief of xerostomia symptoms. Although both dosages of cevimeline provided symptomatic improvement, 60 mg 3 times daily was associated with an increase in the occurrence of adverse events, particularly gastrointestinal tract disorders. Use of 30 mg of cevimeline provides a new option for the treatment of xerostomia in Sjögren syndrome.
Hmmm, looks like pilocarpine has less CNS side effects when administered orally:
Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.
Omori Y, Asari T, Maruyama K, Kusama H, Kojima M, Shibata N.
Clinical Development, Kissei Pharmaceutical Co., Ltd., Hotaka, Nagano, Japan.
The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.1-0.8 mg/kg i.d.) and cevimeline (3-30 mg/kg i.d.) dose-dependently increased salivary flow rate and total salivary volume in a 120-min period from SM/SL glands in both normal and irradiated rats, the minimum effective doses for their sialagogic effects being 0.2 and 10 mg/kg, respectively. Both drugs also increased protein output from SM/SL glands to a degree that depended on the increase in salivary volume in normal and irradiated rats. In a binding study using radiolabeled antagonists, neither pilocarpine hydrochloride nor cevimeline displayed subtype selectivity for muscarinic receptors, indicating non-selective muscarinic agonism. Effects on the central nervous system (CNS) were assessed by monitoring changes in body temperature in conscious normal rats. Pilocarpine hydrochloride (0.4-4 mg/kg p.o.) had no effect on body temperature, but cevimeline (30 and 100 mg/kg p.o.) caused a significant hypothermia. In terms of respiratory and cardiovascular effects in anesthetized normal rats, there was no clear difference in safety margin between pilocarpine hydrochloride and cevimeline, both drugs inducing significant changes in respiratory rate, heart rate, and blood pressure at doses close to those inducing sialagogic effects. These results suggest that pilocarpine hydrochloride could be used as a sialagogic drug for postirradiation-induced xerostomia with fewer adverse effects on the CNS.
PMID: 12854361 [PubMed - indexed for MEDLINE], http://www.ncbi.nlm....pubmed/12854361
But a cevimeline gargle might produce the desired effect minus the unpleasant sides, though this source doesn't comment on the duration of the effect:
Cevimeline gargle for the treatment of xerostomia in patients with Sjogren's syndrome
Y Takagi, Y Kimura, T Nakamura
...To overcome these disadvantages of oral doses of cevime- line, we evaluated the efficacy of cevimeline gargle for the treatment of xerostomia in patients with Sjogren's syndrome. We first evaluated the effect of the gargle in 11 healthy female volunteers (mean (SD) age 39 (13) years, range 19–57), after approval from the ethical committee of our hospital. The volunteers were asked to gargle three times a day before meals using 30 mg cevimeline dissolved in 100 ml of water for each session. The effects of treatment were evaluated daily by a Saxon test performed at around 3 00 pm. Most of the healthy subjects responded well to the cevimeline gargle, and the salivary flow rate gradually increased, reaching an 81% increase on average by day 5. Some subjects showed more than twofold increases in salivary flow after cevimeline gargle. No adverse effect was seen. Simple gargles without cevimeline had no effect...
Free full text: http://www.ncbi.nlm....les/PMC1755032/
Ultimately, if you could address the underlying cause of your mouth breathing, that would probably be ideal vis a vis avoiding drug side effects. Not to mention, chronic nasal inflammation from allergy or infection can't be good for longevity.
Niner's suggestions are great, however I'd be wary of antihistamines at this stage, as they could exacerbate your dry mouth. You might look into steroidal nasal sprays, which seem to have a good efficacy:side effects ratio, as does nasal irrigation. I don't know if you've done this, but you might ask your doctor to look for a structural cause, e.g. deviated septum or nasal polyps. If none of that works, I'd try gargling with pilocarpine or cevimeline.
Best of luck to you; I hope you can resolve this and get your quality of life back!