TCPR: What’s the best way to manage side effects: lower the dose of the current medication or use an antidote?
Dr. Mago: If the patient can stay well on a lower dose, that’s usually my first approach. Most side effects are dose related.

TCPR: For the rest of this interview, we’ll assume that lowering the dose or changing the medication was not feasible or effective for our patients. Let’s cover a few common side effects. What can you tell us about nausea?

Nausea

Dr. Mago: Nausea is one of the top reasons that patients stop medications prematurely. That’s unfortunate because nausea usually subsides in a little bit of time. We can also reduce the incidence of nausea greatly by starting at a low dose and titrating slowly, like after 1 week. In randomized trials, that strategy tends to cut the rate of nausea in half. When nausea does happen, we need to step in energetically with solutions. I tell the patient, “Listen, I understand that this is bothersome. We are going to do something about it today, but I can reassure you the nausea is not harming your body.”

TCPR: Then what do you tell the patient?
Dr. Mago: First, the patient needs to take the medicine after food. Not with food, but immediately after a meal. Taking inger root is another strategy. This is not just an old wives’ tale—there are several randomized placebo-controlled trials of ginger extract for nausea associated with chemotherapy or pregnancy (Bodagh et al, Food Sci Nutr 2019;7(1):96–108).

TCPR: What about ginger ale?
Dr. Mago: No, even if a brand says “contains real ginger” like Canada Dry now does, the amount of ginger in soft drinks is too low—about 50 times lower than what is used in clinical trials. I recommend ginger capsules, about 1 hour before eating. That gives the ginger time to absorb. Then patients should take their medication immediately after eating. Good brands include Vitamin Shoppe, Nature’s Way, and Nature’s Bounty. The standard dose for the 550 mg capsules is either 2 capsules once a day or 1 capsule 2–3 times a day. One can increase it, but we should not assume that ginger is completely benign. I usually don’t exceed 3 capsules a day (1,650 mg).

TCPR: What’s your second and third line for nausea?
Dr. Mago: Ondansetron (Zofran) works well and actually blocks the 5-HT₃ receptor, which is the cause of nausea with most serotonergic medications. It’s a “clean” drug in terms of its receptor effects with limited side effects of its own, but constipation is possible. I use the orally disintegrating tablets, starting with 4 mg, and will raise the dose to 8 mg if needed. If that does not work, metoclopramide is another option for the treatment of nausea (10 mg po q8hr prn).

Sweating

TCPR: You’ve done a lot of research on sweating. What do you find useful?
Dr. Mago: Sweating is something we see with almost all antidepressants, and it’s very bothersome to the patient. Glycopyrrolate is my first choice and works very well (Mago R, J Clin Psychopharmacol 2013 33(2):279–280). It’s an anticholinergic that does not cross the blood-brain barrier, so it won’t impair cognition. That’s a problem with centrally acting anticholinergics like oxybutynin and benztropine (Cogentin). Glycopyrrolate can have peripheral anticholinergic side effects, though, like constipation and dry mouth. Actually, that last one makes it useful for clozapine-induced drooling, and it’s my first choice for that problem as well. Glycopyrrolate is dirt cheap, and you can take it prn. I dose it 1 mg, 1–2 po q6hr prn.

TCPR: What about terazosin, the alpha-1 antagonist?
Dr. Mago: Yes, there are two ways to treat sweating. You can block the effect of acetylcholine at the level of the sweat gland with an anticholinergic, or block the effect of norepinephrine at sympathetic ganglia with an alpha-1 antagonist. There’s an interesting reason behind that. The sweat gland is the only gland in the body where the upper and lower motor neurons use different neurotransmitters: norepinephrine in the upper motor neuron, and acetylcholine in the lower motor neuron. Terazosin works very well, but has a couple of disadvantages. One is a small risk of hypotension, especially with the first dose, which means it cannot be taken on an as-needed basis.

TCPR: When do you use anticholinergics that do cross the blood-brain barrier, like benztropine (Cogentin)?
Dr. Mago: Not for sweating, because the cognitive side effects usually outweigh the benefits. But they are useful for antipsychotic-induced parkinsonism, because there you need a central mechanism for what you are trying to treat (parkinsonism). But still, the cognitive side effects are a bigger problem than is commonly realized (Lupu AM et al, J Clin Psychiatry 2017;78(9):e1270–e1275).

Dry mouth

TCPR: We see dry mouth with nearly all medications, particularly anticholinergics, antipsychotics, and tricyclics. Why is this important to address?
Dr. Mago: Dry mouth is not just uncomfortable. Saliva protects the teeth, so dry mouth can lead to significant problems like dental cavities. People with mental health problems are three times as likely to lose all their teeth than the general public, and dry mouth is one of the main reasons for that. Dry mouth can also be socially embarrassing. It causes bad breath. Also, others may notice patients with dry mouth licking their lips and sucking in their cheeks. Here’s an important point: Other things being equal, anything that is socially embarrassing is more likely to affect adherence to medication. On the other hand, a lot of patients don’t actively complain about dry mouth, but even mild cases can be problematic if they go on too long. So I’m proactive. I tell the patient, “Even though you don’t think it’s that important, it’s worth addressing because otherwise you may get cavities.”

TCPR: How do you address it?
Dr. Mago: First, protect the teeth. Ensure that the patient is getting frequent dental cleanings. A cleaning every 3 months would be ideal, but insurance won’t cover that frequency, so the patient would have to pay for it out of pocket. Regular flossing and brushing the teeth at least twice a day are absolutely essential. Avoid mouthwashes that contain alcohol (like Listerine) because they may make dry mouth worse. I also recommend that patients take sips of water while eating. Doing so will enhance the taste of food and make it easier to swallow, both of which can be problems for people with dry mouth.

TCPR: What do you do after those basic steps?
Dr. Mago: One thing that really helps—both with dental hygiene and halitosis (bad breath)—is xylitol. This is a natural sugar that bacteria consume and cannot metabolize. It lowers the bacterial count in the mouth. Xylitol is available in chewing gums, lozenges, and sprays. The chewing gum also mechanically cleans the teeth. One important detail is that xylitol products must be used no less than 4 times a day to have a significant effect on the bacterial count in the mouth (Villa A et al, Ther Clin Risk Manag 2014;11:45–51).

TCPR: What are some specific products?
Dr. Mago: Spry and Epic are brands that I recommend, but there are others. Xylitol-containing products are relatively cheap. You’ll find them in almost all pharmacies and grocery stores next to the toothpaste and mouthwashes.

TCPR: What about Biotene products?
Dr. Mago: Biotene is a saliva substitute that moisturizes the mouth. It provides symptom relief, but it doesn’t kill bacteria. I usually recommend the mouthwash or the gel. The mouthwash can be used at night, which might make sleeping a bit more comfortable; using a humidifier in the bedroom can also help with that. The Biotene gel has the advantage of being easy to carry around and use at any time of day. You squeeze a small amount out on your tongue and move your tongue to spread it around.

TCPR: Do you ever use medications for dry mouth?
Dr. Mago: There are two FDA-approved medications for dry mouth: cevimeline and pilocarpine. I never prescribe them because they have significant cholinergic side effects like diarrhea, but they are useful for medical conditions like Sjögren’s syndrome, which can cause severe dry mouth. I use a different strategy with these to avoid systemic side effects. I’ll prescribe pilocarpine in the eye drop formulation at the highest strength (4%) rather than the tablets. Add a few of those drops to half a teaspoon of water and swish it around in the mouth. Next, and this is important, I tell the patient to spit it out to avoid systemic side effects. It’s a good localized treatment for dry mouth and can be used as needed. Pilocarpine is generic and very affordable.

TCPR: Thank you for your time, Dr. Mago.

Editor’s note: We’ll continue this interview in our August issue, addressing hair loss, weight gain, akathisia, and orthostasis. Practical tips on a wide variety of topics in psychopharmacology from Dr. Mago are available on his website at www.simpleandpractical.com.