Table 2.
Medications reported to induce xerostomia, salivary gland hypofunction, or sialorrhea with higher level of evidence
| Drug name | ATC code | Mechanism and site of action | Number of citations for | Sources per level of evidence (n) | Total publications (n) | References | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Oral ‘dryness’ | Sialorrhea | |||||||||||||
| Xerostomia | SGH | Subjective | Objective | A1 | B1 | A2 | B2 | A3 | B3 | |||||
| Alendronate (anti-bone-resorptive activity) | M05BA04 | Bisphosphonate—inhibits osteoclastic bone resorption | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | [13] |
| Amitriptyline (anti-depressant) | N06AA09 | Non-selective 5-HT/NE reuptake inhibitor, anti-muscarinic | 5 | 1 | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 1 | 6 | [14–19] |
| Aripiprazole (atypical anti-psychotic) | N05AX12 | Dopamine stabilizer; partial dopamine (D2) and 5-HT1A agonist, 5-HT2A antagonist | 5 | 0 | 0 | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 5 | [20–24] |
| Atropine (GI disorders/mydriatic) | A03BA01, S01FA01 | Anti-muscarinic | 3 | 2 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 4 | [14, 25–27] |
| Baclofen (skeletal muscle relaxant—centrally acting) | M03BX01 | GABA agonist: reduces release of excitatory glutamate | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [28] |
| Bendroflumethiazide (weak diuretic) | C03AA01 | Inhibits reabsorption of NaCl in distal tubule of nephron | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | [29] |
| Bevacizumab (anti-neoplastic) | L01XC07 | Monoclonal antibody: inhibits vascular proliferation and tumor growth | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [30] |
| Brimonidine (anti-glaucoma) | S01EA05 | α2-Adrenergic agonist | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 3 | [26, 31, 32] |
| Buprenorphine (opioid-analgesic) | N02AE01, N07BC01 | Mixed receptor actions; κ-opioid antagonist and partial µ-opioid agonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [33] |
| Bupropion (anti-depressant) | N06AX12 | NE/dopamine reuptake inhibitor | 12 | 0 | 0 | 0 | 0 | 5 | 0 | 3 | 0 | 4 | 12 | [34–45] |
| Butorphanol (opioid-analgesic) | N02AF01QR05A90 | Mixed receptor actions; κ-agonist and µ-antagonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [46] |
| Chlorpromazine (anti-psychotic) | N05AA01 | Antagonist to dopamine, 5-HT, histamine (H1), muscarinic and α(1,2)-adrenergic receptors | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [47] |
| Citalopram (anti-depressant) | N06AB04 | Selective 5-HT reuptake inhibitor | 3 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 3 | [34, 48, 49] |
| Clonidine (anti-hypertensive/anti-migraine) | C02AC01, N02CX02 | α2-Adrenergic agonist | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 4 | 6 | [14, 50–54] |
| Clozapine (atypical anti-psychotic) | N05AH02 | Dopamine antagonist, partial 5-HT and partial muscarinic (M1) agonist, muscarinic (M3) antagonist, and α1-adrenergic antagonist | 2 | 0 | 0 | 7 | 3 | 2 | 1 | 2 | 1 | 0 | 9 | [55–57 a, 58–61 62 a, 63] |
| Cyclobenzaprine (skeletal muscle relaxant—centrally acting) | M03BX08 | Histamine (H1) and muscarinic antagonist | 4 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 3 | [64–66] |
| Dexmethylphenidate (psychostimulant—ADHD) | N06BA11 | Indirect sympathomimetic and NE/dopamine reuptake inhibitor | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [67] |
| Dimebon (anti-dementia) | ND | Unknown action—proposed histamine (H1) and 5-HT antagonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [68] |
| Doxylamine (hypnotic) | R06AA09 | Anti-histamine; histamine (H1) and muscarinic antagonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [69] |
| Duloxetine (anti-depressant) | N06AX21 | 5-HT/NE reuptake inhibitor | 19 | 0 | 0 | 0 | 0 | 1 | 0 | 10 | 0 | 8 | 19 | [34, 70–87] |
| Escitalopram (anti-depressant) | N06AB10 | Selective 5-HT reuptake inhibitor | 4 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 4 | [34, 84, 88, 89] |
| Fluoxetine (anti-depressant) | N06AB03 | Selective 5-HT reuptake inhibitor | 9 | 1 | 0 | 0 | 0 | 2 | 1 | 3 | 0 | 3 | 9 | [17, 34, 48, 90–95] |
| Furosemide (strong diuretic) | C03CA01 | Inhibits NaCl reabsorption in the thick ascending loop of Henle | 2 | 3 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 3 | [14, 29, 96] |
| Gabapentin (anti-convulsant) | N03AX12 | Proposed action: stimulates GABA synthesis and GABA release | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [97] |
| Imidafenacin (urological—reduces bladder activity) | ND | Anti-muscarinic | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [98] |
| Imipramine (anti-depressant) | N06AA02 | 5-HT/NE-reuptake inhibitor, antagonist to histamine (H1), 5-HT, muscarinic and α1-adrenergic receptors | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | [99, 100] |
| Lisdexamfetamine (psychostimulant—ADHD) | N06BA12 | 5-HT/NE reuptake inhibitor | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | [101, 102] |
| Lithium (anti-psychotic) | N05AN01 | Mood stabilizer; inhibits dopamine/NE release and intracellular Ca2+ mobilization | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 4 | [103, 104–106] |
| Loxapine (anti-psychotic) | N05AH01 | Dopamine/5-HT antagonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [107] |
| Methylphenidate (psychostimulant—ADHD) | N06BA04 | Indirect sympathomimetic, release of dopamine, and NE/5-HT reuptake inhibitor | 5 | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 1 | 5 | [37, 108–111] |
| Nortriptyline (anti-depressant) | N06AA10 | NE reuptake inhibitor, antagonist to histamine (H1), 5-HT, α1-adrenergics, and muscarinics | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | [97, 112] |
| Olanzapine (atypical anti-psychotic) | N05AH03 | Antagonist to dopamine, 5-HT, histamine, muscarinics, and α1-adrenergics | 10 | 0 | 0 | 1 | 0 | 4 | 1 | 5 | 0 | 1 | 11 | [20, 56, 113–120 a, 121] |
| Oxybutynin (urological—reduces bladder activity) | G04BD04 | Anti-muscarinic | 20 | 3 | 0 | 0 | 0 | 7 | 0 | 10 | 0 | 4 | 21 | [122–142] ([138–140] are animal studies) |
| Paliperidone (atypical anti-psychotic) | N05AX13 | Antagonist to dopamine, 5-HT, α(1,2) –adrenergics, and histamine | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | [143, 144] |
| Paroxetine (anti-depressant) | N06AB05 | 5-HT reuptake inhibitor | 3 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 3 | [34, 41, 145] |
| Perphenazine (anti-psychotic) | N05AB03 | Antagonist to 5-HT, dopamine, histamine (H1), muscarinic, and α1-adrenergic receptors | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [113] |
| Phentermine (appetite suppressant) | A08AA01 | Releases NE and to a lesser degree dopamine and 5-HT | 3 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 3 | [146–148] |
| Propantheline (anti-peristaltic/spasmolytic) | A03AB05 | Anti-muscarinic | 2 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 3 | [14, 129, 133] |
| Propiverine (urological—reduces bladder activity | G04BD06 | Anti-muscarinic | 5 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 2 | 6 | [98, 127, 129, 133, 134, 149 a] |
| Quetiapine (atypical anti-psychotic) | N05AH04 | Dopamine, 5-HT, α(1,2)-adrenergic, and histamine (H1) antagonist | 14 | 0 | 2 | 0 | 0 | 12 | 0 | 1 | 0 | 1 | 14 | [103, 113, 116 144, 150–159] |
| Reboxetine (anti-depressant) | N06AX18 | NE reuptake inhibitor, anti-muscarinic | 5 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 2 | 5 | [85, 160–163] |
| Risperidone (anti-psychotic) | N05AX08 | Antagonist to dopamine, serotonin, histamine (H1), and α1,2 adrenergic receptors | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | [113, 164] |
| Rotigotine (anti-Parkinson) | N04BC09 | Dopamine and 5-HT agonist, α2 adrenergic antagonist | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | [165, 166] |
| Scopolamine (anti-nauseant/sedative/GI disorders) | A04AD01, N05CM05 A03BB01 | Muscarinic antagonist | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 3 | [14, 167, 168] |
| Sertraline (anti-depressant) | N06AB06 | 5-HT reuptake inhibitor | 4 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 1 | 4 | [34, 48, 93, 95] |
| Sibutramine (anti-depressant) | A08AA10 | Reuptake inhibitor of NE/5-HT/dopamine | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | [169, 170] |
| Solifenacin (urological—reduces bladder activity) | G04BD08 | Anti-muscarinic | 9 | 2 | 0 | 0 | 0 | 2 | 0 | 5 | 4 | 0 | 11 | [133, 134, 137–139, 171–176] |
| Tesofensine (appetite suppressant) | ND | NE/5-HT/dopamine reuptake inhibitor | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [177] |
| Timolol (anti-glaucoma) | C07AA06 | Non-selective β-adrenergic antagonist | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | [32] |
| Tiotropium (anti-asthmatic) | R03BB04 | Prevents bronchoconstriction, anti-muscarinic | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | [178, 179] |
| Tolterodine (urological—reduces bladder activity) | G04BD07 | Anti-muscarinic | 19 | 2 | 0 | 0 | 0 | 4 | 1 | 10 | 1 | 3 | 19 | [124, 128, 129, 133–135, 138, 142, 180–190 a,191] |
| Venlafaxine (anti-depressant) | N06AX16 | NE/5-HT reuptake inhibitor | 8 | 0 | 0 | 1 | 0 | 1 | 0 | 7 | 0 | 0 | 8 | [17, 34, 52, 89, 192–195 |
| Verapamil (anti-hypertensive/anti-angina) | C08DA01 | Calcium channel blocker—arterial vasodilator effects | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 196] |
| Vortioxetine (anti-depressant) | N06AX26 | 5-HT reuptake inhibitor | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | [75, 197] |
| Ziprasidone (atypical anti-psychotic) | N05AE04 | 5-HT, dopamine and α-adrenergic antagonist | 3 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 3 | [113, 198, 199] |
| Zolpidem (hypnotic/sedative) | N05CF02 | Agonist at the benzodiazepine site of the GABAA receptor, enhancing the inhibitory effect of GABA | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 2 | [200, 201] |
5-HT 5-hydroxytryptamine (serotonin), ADHD attention-deficit/hyperactivity disorder, ATC Anatomical Therapeutic Chemical, GABA gamma-aminobutyric acid, GI gastrointestinal, ND not determined, NE norepinephrine, SGH salivary gland hypofunction
aAnimal studies