27. Medication Side Effects

In this chapter, we’ll first summarize the information about side effects we’ve already mentioned. We’ll then review key questions you should ask yourself if you think you may be experiencing a medication side effect. Finally, we’ll describe how to manage those which are most common.

When deciding if a medication should remain in your living treatment plan, you need to consider its effectiveness, its side effects, and treatment alternatives. Giving up on a medication because of a mild side effect may keep you away from an effective treatment. At the same time, don’t accept a bothersome side effect without at least discussing it with your doctor. You may be suffering needlessly.

Our key message is this: treatment is a balancing act, so talk to your doctor about your medication side effects.

General Strategies

Over the last few chapters, you’ve already learned a few important things about side effects:

• Just because a medication may cause a side effect does not mean you will have that side effect. A common side effect is one that affects fewer than 1 in 10 people taking a medication and maybe as few as 1 in 100. Those are pretty good odds.

• Side effects vary in severity, from barely there, to noticeable, to slightly annoying, to completely debilitating. The severity of a side effect should influence what action you take, if any.

• Most side effects occur within the first few days of starting a medication or when changing the dose. Most decline over several days to a couple of weeks. They may disappear entirely given enough time.

• Your expectations affect how you experience side effects. If you anticipate a terrible ordeal, you are more likely to find side effects more intense or bothersome. Side effects can be caused by anxiety, instead of the medication.1

• Similar medications can have vastly different side effect profiles.

We’ve discussed these approaches to managing side effects:

• Wait. Wait some more. Then wait some more. There may be no point dealing with something that will disappear over time.

• Go lower and slower. If you have side effects when increasing the medication dose, increase the dose by a smaller amount and at a slower rate. This also applies if you have withdrawal when decreasing the dose. The standard dosing schedules are too aggressive for many people. The next chapter discusses options, such as splitting pills or compounding, if smaller doses aren’t commercially available.

• Change how you take the medication. Would taking it at a different time of day help? If it causes fatigue, take it in the evening. Does taking it with or without food make a difference? What about splitting one large dose into two smaller ones taken at two separate times?

• Does a slightly lower dose reduce side effects? If so, how much does that worsen symptoms? Could boosting or augmenting the lower dose with another medication help? Consider non-medication treatments that could reduce how much medication you need, e.g., diet, sleep, exercise, and therapy.

• Can you work around the side effects? In other words, are there things you can do to avoid or minimize them? You might add another medication or natural supplement to treat the side effect. Or are there behaviour changes that could help? For example, improving your sleep hygiene can reduce the impact of medication-induced insomnia.

• Try another medication? Weigh the cost of the side effect, the benefit from the medication, the time needed to slowly stop the current medication, and the risk involved with another medication. If the side effect is greatly impacting your life and is tough to work around, trying another medication is probably the right answer.

Get Help or Wait?

Usually, waiting to see if a side effect will resolve on its own is the right thing to do. But that’s not always the case. Some things, typically quite rare, need to be dealt with right away. These include a severe allergic reaction or passing out from a large drop in blood pressure.

Don’t toss the information leaflet the pharmacist gives you when you pick up your medication. It tells you what to do if you encounter specific side effects. You may need to immediately stop it, seek medical attention, or call your doctor or pharmacist for advice. If you did throw away the information, you can find patient medication handouts on consumer websites such as drugs.com or rxlist.com.

Some medications have side effects which aren’t urgent but can be serious if not dealt with. For example, the anticonvulsants lamotrigine or carbamazepine can cause a rash. Left untreated, some rashes could develop into Stevens-Johnson Syndrome, which can sometimes be fatal over time. When starting these medications, your doctor or pharmacist will usually tell you what to watch for and what to do if a rash appears.

Waiting is the right approach when dealing with most side effects. If in doubt, ask your pharmacist or doctor.2 When you describe your side effects, try to be as specific as possible.

Sexual Dysfunction

Some side effects concern people more than others and can deter them from starting a medication. Sexual side effects are high on that list. They are also a frequently given reason that medications are stopped prematurely.

Sexual side effects usually fall into one or more of three categories. The first is reduced sexual desire or libido. The second is a decrease in arousal. Men have difficulty developing or maintaining an erection. Women experience inadequate lubrication and swelling of their genitals. The third is greater delay or difficulty reaching orgasm or inability to orgasm.

Much of the general advice applies to sexual dysfunction. Changes in dose and timing can help, as can increasing exercise and decreasing alcohol use. A similar medication may not cause you problems, even if it also carries a risk of sexual side effects. Sexual problems can also be caused by other stressors or be symptoms of a mental or physical illness needing further treatment. If sexual side effects occur, they may diminish over time. Unfortunately, this is less likely than with side effects such as nausea or headache.

Beyond the general approaches to side effects, there are several options to consider.3 Each has benefits and risks that depend on your situation and physical health. Discuss these with a family doctor or psychiatrist who knows all aspects of your health:

• The antidepressant bupropion (Wellbutrin) is widely used to reduce or counteract the full range of sexual side effects of other medications. It can, however, increase anxiety, irritability, and, for those with a bipolar disorder, rarely precipitate a hypomanic or manic episode.

• For men, medications such as sildenafil (Viagra) and tadalafil (Cialis) can usually resolve erectile problems. While there have been suggestions that these medications may have some benefit for women, evidence either supporting or refuting this is limited.

• Problematic medications can be temporarily decreased or stopped for a few days during so-called medication holidays. These may temporarily reduce sexual side effects but only work for medications with a moderate half-life. They don’t work for medications such as fluoxetine (Prozac) that stay in your system for many weeks after you stop it. They also may not work with medications such as venlafaxine (Effexor) or paroxetine (Paxil) which leave your system quickly when stopped and thereby cause severe withdrawal. Medication holidays increase the risk of your mental health deteriorating or premature discontinuation of your medication altogether.

• Several other medications reduce sexual side effects when taken before sex. Their effectiveness and clinical evidence vary. These include the antihistamine cyproheptadine, the anxiolytic buspirone (Buspar), the alpha-adrenergic blocker yohimbine, the antiparkinsonian amantadine, and stimulant medications for ADHD.

• A few natural supplements have also been used to reduce the impact of sexual side effects. What limited clinical evidence is available is mainly in the form of case reports. Common supplements include natural yohimbine extracts, maca root, ginkgo biloba, and saffron. Acupuncture has some limited evidence for use in this context.

Weight Gain

Possible weight gain is a concern with many medications, psychotropic medications among them. It’s most common with antipsychotic and some mood stabilizing medications. Some people feel severe anguish at the thought of taking any medication that may cause weight gain. If this is a concern, have a frank conversation with your doctor up front. Emphasize the importance of addressing any weight gain. As always, even though weight gain can occur, it doesn’t mean it will. It’s worth noting that weight gain can be a symptom of depression and other mental illnesses. Many people also put on weight from binge eating to cope with their distress.

Weight gain can lead to many health conditions, including cardiovascular disease and diabetes. Signs to watch for include high blood pressure, high blood glucose levels, excess fat in the abdominal area, and abnormalities in cholesterol and triglycerides. Baseline measurements should be taken before starting a medication with a high potential for weight gain. Periodic measurement while you’re taking the medication should catch any changes early. They then can be addressed before they turn into serious health issues.

One option to deal with weight gain is switching to another medication. That, of course, carries its own challenges. As with weight gain from other causes, behavioural modification, such as changes in diet, exercise, and education around nutrition is preferred. Some forms of cognitive behavioural therapy and mindfulness are also effective.

Sleep Problems

Problems falling or staying asleep are both symptoms of some mental illnesses. They are also side effects of some psychotropic medications. Unfortunately, sleep issues can worsen your mental health. But, a variety of approaches can help.4 Adjusting when you take a medication may be enough. For instance, take a more stimulating medication earlier in the day.

Medications or supplements can be a short-term solution. Over-the-counter products such as antihistamines and short-acting or long-acting melatonin are commonly helpful. Your doctor might prescribe a benzodiazepine or a z-drug such as zolpidem or zopiclone. These can be problematic when used long term. Sedating antidepressants are frequently prescribed along with other medications to help with sleep. Trazodone, doxepin, and mirtazapine are the most common of these. The older antihistamine hydroxyzine is also used. Both the blood pressure medication prazosin and the antipsychotic quetiapine can reduce nightmares. These add-on medications may help you but have their own side effects.

If you have long-term sleep issues, however, prescription and over-the-counter medications and supplements are usually not the answer. The best solution is improving your sleep hygiene. This collection of habits and practices was described in the Lifestyle Factors chapter. Another option is a specific form of cognitive behavioural therapy that has been proven to help with insomnia. If insomnia or fatigue remains problematic, ask your doctor if you need tests for sleep apnea or another sleep disorder.

Anticholinergic Symptoms

One group of symptoms is caused by a decrease in the neurotransmitter acetylcholine, a common effect of many medications, including some psychotropics. These symptoms are therefore termed anticholinergic side effects.5

These include dry mouth, constipation, urinary retention, bowel obstruction, dilated pupils, blurred vision, palpitations, decreased sweating, impaired concentration, brain fog, decreased attention, memory impairment, sedation, and dizziness.

Because so many medications have anticholinergic side effects, family doctors have a lot of experience with managing them. After reviewing your medication list, they can adjust the doses or change them altogether. There are also some medications, e.g., bethanechol, which have a cholinergic effect, increasing acetylcholine and thereby reducing these side effects. Deficiencies of the nutrient choline are also common.6 You may need to address this with diet changes or supplements.

Keep in mind that many anticholinergic symptoms are relatively nonspecific and have multiple other possible causes.

Anticholinergic medications can be deliberately added to counteract other medication side effects. For example, many medications can increase sweating. Anticholinergic medications such as benztropine (Cogentin) can help.

Cognitive Problems

Cognitive side effects include changes in memory, attention, concentration, problem-solving, multitasking, processing speed, and reaction time. These can result from the anticholinergic effects of medications. They also occur with benzodiazepines, antipsychotics, and some anticonvulsants. Medications aren’t always the cause of these problems. They can be due to underlying illnesses such as depression or ADHD. Alcohol or substance use can contribute. So can poor sleep, a lack of exercise, or many dietary deficiencies. Identifying and addressing any of these factors is usually the first step.

After that, identifying and switching or reducing doses of anticholinergic medications such as paroxetine (Paxil), some tricyclic antidepressants, and some antipsychotics is often recommended. Adding other medications may help address cognitive problems in people with depression or anxiety. Most common are psychostimulants. These include amphetamine, methylphenidate, or modafinil. Other medications that increase dopamine, such as some for Parkinson’s disease, or cholinesterase inhibitors, which help cognitive symptoms in Alzheimer’s patients, have been investigated, but trials have been mostly inconclusive.

Twitching and Restlessness

A variety of different side effects related to agitation, restlessness, and muscle twitching can occur. When they happen, they are often benign, but they can become annoying if frequent or severe.

Akathisia is a feeling of inner restlessness. It can make it difficult to sit still. This leads you to fidget, rock back and forth, and repeatedly cross and uncross your legs. Many people feel stressed or irritable and describe wanting to climb out of their skin. Beta blockers such as propranolol (Inderal) are usually the first medications prescribed. Some Parkinson’s medications can also be used. Benzodiazepines such as lorazepam (Ativan) can help, but for short-term use only.

Restless legs often respond well to dopamine agonists such as pramipexole (Mirapex), gabapentin, or pregabalin (Lyrica). Low iron (ferritin BODYlt; 50) can be a contributing factor and must be treated.

Involuntary muscle twitches are usually benign. They can be worsened by dehydration, low magnesium, or low calcium. If intrusive, medications such as propranolol or clonazepam are often used.

A persistent tremor should be evaluated by a doctor. It can be perfectly harmless. It can be due to many physical conditions, some mild, and some serious. It may be an indication of medication toxicity.

Others

Over-the-counter treatments are readily available for many side effects, at least in the short term:

• Headaches and other pain may be relieved with a wide range of over-the-counter medications, e.g., Tylenol, Advil.

• For dry mouth, try chewing sugarless gum, or using a product such as Biotene.

• Diarrhea or constipation may respond to diet changes (e.g., adding fibre), or medications such as bismuth subsalicylate (Pepto-Bismol), loperamide (Imodium), or PEG 3350 (Miralax). Be aware that some of these products affect how you absorb medication; check with your pharmacist.

• For nausea, try ginger products or bismuth subsalicylate. Dimenhydrinate (Gravol/Dramamine) has a strong anticholinergic effect, and so may or may not be advised.

Prescription medications are also available for the above concerns. For example, both ondansetron (Zofran) and mirtazapine (Remeron) affect the serotonin receptors that cause most psychotropic-induced nausea. If over-the-counter preparations aren’t sufficient, ask your doctor.