How do you manage the side effects of SSRIs?

What do you do when a patient taking an SSRI presents with anorgasmia, bruxism, or hyponatremia? Firstly – believe your patient. Your 60 yo may experience an increase in suicidal thoughts even though the textbook says that she shouldn’t. In general, your options for managing side effects from medication are:

  1. Watchful waiting
  2. Change the time the medication is given
  3. Lower the dose
  4. Add another medication to treat a specific side effect
  5. Change the medication 

The balance between the medication benefits and side effects for an individual patient determines the next steps. We may tolerate more severe side effects if a medication is very effective, and prior options were not. A patient’s perception of the balance between efficacy and side effect burden is generally more important than the objective severity of a particular side effect.

Below are 3 cases to illustrate application of this framework to SSRI side effects and a summary table about managing the side effects of SSRIs.


Grace is a 37 yo woman who presents in a severe major depressive episode. In addition to connecting her with therapy, you start sertraline and titrate the dose to 150mg over 3 weeks due to the severity of her symptoms. One week after she gets to sertraline 150mg daily, her depressive symptoms start to improve. Two months later, she no longer feels depressed. “But,” she says, “There’s just one thing. I don’t know how to describe it, but it feels like I’m further away from life – I’m not sad but I’m also not excited about anything. It’s like the intensity of all my emotions has been turned down.” What do you recommend?

Emotional numbing or apathy is a common side effect of serotonergic medications, including the SSRIs. It is often dose dependent. I would reduce the dose of sertraline to 100mg daily as a first step, while monitoring her depressive symptoms carefully. Hopefully there is a dose of sertraline between 50 and 100 mg that keeps Grace’s depression in remission but allows her to feel her feelings. If that sweet-spot cannot be found, I would discuss the risks and benefits of switching from sertraline to bupropion vs staying with sertraline. Switching to bupropion, which is not a serotonergic medication, should resolve the SSRI-induced apathy, but carries a higher risk of depressive relapse. Continuing maintenance treatment with antidepressants for at least 6 months from the point of remission for a first major depressive episode is important to prevent depressive relapse.



Jesse is a 28 yo man with recently diagnosed depression who started escitalopram 10mg three months ago. Jesse’s mood improved, but he sweats all the time, and it’s interfering with work and sleep. To him, the sweating seems directly connected to starting escitalopram. What do you recommend?

Sweating is a common side effect of SSRIs with case reports estimating its prevalence at 4-22% for patients on these medications (March 2005). Following the algorithm above, you have options – lower the dose, add something else to treat the side effect, or change the med. Jesse opts to treat the sweating specifically. 

Sweating is influenced by environmental factors like temperature and humidity. Non-medication interventions can be helpful, like wearing exercise clothes to bed that wick sweat or using a fan at night. Medications can also help; some patients need a daily medication while others may only sweat on certain days and use a PRN medicine. The adrenergic actions of antidepressants are thought to cause sweating, which is why SNRIs commonly cause more sweating than SSRIs. Alpha and beta blockers and serotonergic antagonists like cyproheptadine can improve sweating, but their side effect profiles limit their clinical utility (Kolli 2013). Anticholinergic medications are effective treatments for excessive sweating because the sweat glands have cholinergic innervation. The anticholinergic medicine glycopyrrolate does NOT cross the blood-brain barrier to a significant extent (unlike benztropine) which is why case reports support its preferential use to treat sweating (Mago 2013). Generally, patients are started on glycopyrrolate at 0.5 mg BID which can be titrated up to 1 mg BID to help with symptoms. If a patient’s sweating is only during the day or only at night, then glycopyrrolate can be started at 1mg once a day, increasing to 2mg as tolerated. For Jesse, you recommend starting 0.5mg glycopyrrolate twice a day. He notices immediate improvement within the week of starting glycopyrrolate and complete resolution at 1 mg in the morning by week 2.



Louise is a 60 yo woman with depression who started sertraline, titrated to 100mg two months ago. Sertraline improved her depression, and she would like to continue the medication for now. However, she’s recently noticed pain on the right side of her jaw, and her husband reports she started grinding her teeth at night. Her jaw pain limits her ability to eat in the morning. She does not have any headaches, facial numbness or tingling, visual, gustatory, or auditory changes, or difficulty speaking or swallowing. She does drink 1-2 glasses of wine per night; on the nights she drinks, she snores. What do you recommend?

Bruxism is characterized by clenching of the jaw and grinding of the teeth. It can occur during sleep or wakefulness. It is associated with sleep apnea, snoring, and anxiety, as well as with the use of caffeine, alcohol, or tobacco. Given the association between alcohol use, snoring, and bruxism, you recommend that Louise cut down to 0-1 drinks per evening and continue sertraline 100 mg. You ask her husband to monitor her snoring and teeth grinding after making this change. At your 2 week follow up, her snoring has improved but the teeth grinding has not. You worry that this new teeth grinding and jaw pain may be a side effect of sertraline. Bruxism is typically seen 2-3 weeks after beginning the medication or increasing the dose (Garrett 2018). You consider decreasing the dose, stopping the sertraline, or adding on a new medication to treat the bruxism specifically. Louise does not want to stop sertraline, but she is interested in lowering the dose since she is not sure at what dose her depressive symptoms truly went into remission. You recommend lowering the sertraline dose to 75 mg. Within 2 weeks, her symptoms of depression have worsened, and her bruxism remains. At this point, you offer the option of increasing sertraline to 100 mg and adding on buspirone to treat bruxism or switching the antidepressant to escitalopram. While escitalopram has been associated with bruxism too, bruxism has been reported most commonly with fluoxetine, venlafaxine, and sertraline (Garrett 2018). Louise does not want to take a second medication and opts to try escitalopram instead. She begins your suggested cross-titration, and once she completes her treatment with sertraline, her bruxism and jaw pain resolves. Escitalopram provides relief from her depression.


Side effectRecommended management strategiesSpecific medications to add to alleviate side effectSwitch to…
Insomniadose in the morning
watchful waiting
trazodone
z-drugs
mirtazapine
bupropion
Fatiguedose in the evening
watchful waiting
lower the dose
bupropion
less sedating SSRI (fluoxetine or sertraline)

Headache
watchful waiting
lower the dose
switch
common headache remedies (acetaminophen, etc)
Nausea
take with food
watchful waiting
lower the dose
switch
mirtazapine
bupropion
Agitation / restlessness
watchful waiting
lower the dose
switch
mirtazapine
Increased suicidal thoughtsstop the medication
Dry mouthsugarless gum or candies
Weight gainswitch medication if lifestyle modification is not effective after 1 monthbupropion
fluoxetine
Apathylower the dose
switch
bupropion
Bruxismlower the dose
switch
add on medication
buspirone 5-30 mg total, dosed 1-3x per day
Sweatinglower the dose
switch
add on medication
glycopyrrolate
0.5-1 mg BID
(dose in the morning or at bedtime if symptoms are only during day or night)
Hyponatremiastop medication, switch to alternate medication and consider lab monitoringbupropion
mirtazapine
Sexual side effects – anorgasmialower the dose
drug holiday
switch
add on medication
buspirone 15mg BID
trazodone 50 mg
bupropion
mirtazapine
buspirone (if for GAD only)
Sexual side effects – decrease libidolower the dose
drug holiday
switch
add on medication
bupropion, PDE5bupropion
mirtazapine
buspirone (if for GAD only)
*Side effects in italics commonly occur when people start taking the medication and are likely to go away within a week or two if the medication is continued.

Each of the SSRIs (with the exception of citalopram and escitalopram) is a unique medication. While the alternative medications to switch to (commonly bupropion or mirtazapine) have a much lower risk of that particular side effect, it may still make sense to stick with the SSRI class. For example, a patient with severe GAD and obesity who is switching from one SSRI due to side effects would be better served by trying a second SSRI than by switching to a medication like bupropion that does not treat GAD, or a medication like buspirone that has a smaller effect size for GAD. While all of the SSRIs can cause side effects, a patient who experiences a side effect from one SSRI will NOT necessarily have the same experience with another one. 

Look out for another PsychSnap this year that will dive deeper into the evaluation and management of sexual side effects of antidepressants.



References:

Marcy TR, Britton ML. Antidepressant-induced sweating. Ann Pharmacother. 2005 Apr;39(4):748-52.

Kolli V, Ramaswamy S. Improvement of antidepressant-induced sweating with as-required benztropine. Innov Clin Neurosci. 2013 Nov;10(11-12):10-1. 

Mago, Rajnish MD. Glycopyrrolate for Antidepressant-Associated Excessive Sweating. Journal of Clinical Psychopharmacology. 2013 Apr;33(2):279-280.

Garrett, AR, Hawley JS. SSRI-associated bruxism, A systematic review of published case reports. Neurology: Clinical Practice. 2018 Apr;8(2):135-141.


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