Now that we’ve talked about psychotropic medications in general, let’s get a bit more specific. This chapter covers antidepressants, which constitutes a broad and varied category of medications.
Antidepressants are far more complicated to take than medications you may be familiar with. How do they work? What do they help with? What should you expect? How long do you take them for? The answers are not always straightforward, leaving many people mystified. Suboptimal use is widespread.
Broadly speaking, the many antidepressants are more similar than different. Understanding what they have in common is 90% of the battle. You’ll learn all about that here. For the last 10%, Appendix C briefly describes individual antidepressants, pointing out what makes each one unique.
By the end of this chapter, you’ll better understand when antidepressants are used, when they shouldn’t be used, and how they work. You’ll also learn how you and your doctor can select specific antidepressants for your particular situation. Most importantly, if you do try an antidepressant, you’ll make smart decisions and have a realistic idea of what to expect.
Despite the name, antidepressants are not only used for depression. They treat many mental health disorders. They are the preferred medications for most forms of anxiety, obsessive-compulsive disorders, trauma, impulsivity, and some eating disorders, to name a few. They are used for several non-mental health issues, including pain management and even irritable bowel syndrome.
If you’re considering taking an antidepressant, read this carefully. Antidepressants are used only with extreme caution if you are prone to episodes of hypomania or mania, which are hallmarks of bipolar disorders. If depressive episodes are periods of very low mood, hypomania and mania are periods of very high mood and energy. According to the DSM-5, these episodes include at least three of the following symptoms:
Inflated self-esteem or grandiosity.
Decreased need for sleep (e.g., rested after 3 hours of sleep).
More talkative than usual or pressure to keep talking.
Racing thoughts or rapidly shifting between ideas (e.g., rambling).
Easily distracted by unimportant or irrelevant things.
Increase in school/work/social activities, or purposeless physical movements driven by mental agitation (e.g., pacing, wringing hands).
Engaging in uncharacteristically high-risk activities (e.g., excessive shopping sprees, sexual practices or relationships).
Full-blown mania will disrupt your life and you may need hospitalization. Hypomania isn’t as severe but still a substantial change from normal. It’s not just a good day. Have you ever had an episode that sounds like this? Did it last most of the day for at least a few days? Tell your doctor, even if it was triggered by medications or illicit drugs. You may have a bipolar disorder or be more prone to hypomania or mania than most people.
Doctors prescribing antidepressants should ask about hypomania or mania, though sometimes this is little more than, “Have you ever spent too much money?” If you suspect past hypomania or mania, speak up, even if you’re not asked. If you are prone to such episodes, an antidepressant increases the risk of another episode. This can happen even if you only had one hypomanic episode twenty years ago. Even if you’re now struggling purely with depression, an antidepressant may not be the right choice. Other medications such as mood stabilizers may be more appropriate.
People who have had hypomania or mania can take antidepressants. It is almost always in combination with a mood stabilizer or other medication. Such a regime is also usually started only under the close supervision of a psychiatrist.
Everyone with a bipolar disorder is different. Some people are primarily depressed and had a single hypomanic episode years ago. Others develop hypomania or mania much more frequently. Using an antidepressant is riskier in the second group than the first, though both groups are at far greater risk than people who have never had such an episode.
The fear of using antidepressants in anyone with a history of bipolar disorders can go to an extreme. We’ve seen several people who carried a diagnosis of a bipolar disorder for decades. Unfortunately, they only had one episode, which didn’t actually meet the criteria for hypomania or mania. The episode wasn’t as severe as once thought, didn’t last more than a short time, or illicit substances were involved (even if they didn’t admit it at the time).
We’ve also seen people labelled bipolar for dozens of years who had seen several psychiatrists. Skeptical, we obtained and carefully reviewed their previous medical records. The first psychiatrist they saw noted “rule out possible bipolar” in their report. That is doctor-speak meaning they didn’t have time to confirm or exclude it. The second read the first note and, based solely on that, diagnosed “possible bipolar.” The third read the second note and diagnosed “bipolar by history.” The fourth read the third note and diagnosed the definitive sounding “bipolar.” This diagnosis was then carried forward indefinitely. This all happened without further discussion or investigation of any past episodes.
Carrying around such a false bipolar diagnosis can affect your current treatment. Avoiding antidepressants may be a tremendous missed opportunity. If something about a longstanding diagnosis doesn’t ring true, try to get a hold of your previous records. You never know what they might reveal.
Like most psychotropic medications, antidepressants affect neurotransmitters. Most often they affect one or more ways of transmitting serotonin (5-HT), norepinephrine (NE), and dopamine (DA).
They use a variety of different mechanisms to influence this transmission. For example, the most common class of medications today are Selective Serotonin Reuptake Inhibitors (SSRIs). As the name suggests, they inhibit (reduce) reuptake of serotonin from the synapse into the nerve’s axon. This increases the chance of binding to serotonin receptors and thus improves signal transmission. Many antidepressants use more than one mechanism and affect more than one neurotransmitter.
Medications within the same class may have similarities but are not interchangeable. And, of course, there are many classes of antidepressants.
For most people, an antidepressant can be one of the most confusing medications they’ve ever taken. Let’s discuss step by step what you need to know.
Antidepressants need to be started at a low dose and slowly increased. This gives your body time to adjust and minimizes side effects. The starting dose and increment vary between medications, but increases are typically at least a week apart. Otherwise, side effects can be more severe and distressing. Starting at too high a dose or increasing too rapidly are major reasons why antidepressants are stopped prematurely. Like many people, you may have decided that you can’t tolerate a medication after a day or two. This may not have happened if you started lower and slower. Unless told otherwise, you assumed the side effects you first experienced would continue as long as you took the medication. However, this is rarely the case, as we’ll discuss shortly.
Some antidepressants won’t have any effect on your symptoms until they reach at least their target dose. The target dose is usually a range, e.g., 20–50 mg. This means that most people who have their symptoms fully relieved by the medication need a dose within that range. This dose varies greatly between medications, so comparing doses of different antidepressants is like comparing apples and oranges. Finding the right dose can be tricky. Too low and the antidepressant only partially helps. Too high and you may have more side effects than you need to experience. It also takes time. Increasing a week at a time may be enough to minimize side effects. It takes longer, typically four to six weeks at a given dose, to feel the full effect. Too many people give up on medications long before they’ve had a chance to work.
Most antidepressants have a recommended dosing schedule, specified in the product monograph (the prescribing information given to doctors). Actual practice often differs. And some individuals are more sensitive to medications. They may need an even lower starting dose, and smaller and slower increments. Most antidepressants have a preferred, once-daily extended-release version. Sedating antidepressants are usually taken at night, and more stimulating ones in the morning. If you find a normally sedating one is stimulating, adjust the time accordingly. You may find that instead of one large dose a day, you have fewer side effects if you split your total dose into two small doses taken at different times.
Too many doctors are unable (or unwilling) to spend the time needed to explain all this when they first prescribe you an antidepressant. If you don’t know what to expect, you’re far more likely to suffer as a result.
What does starting an antidepressant look like in practice? Consider the typical dosing regime for the antidepressant sertraline (Zoloft). It has a target dose of 50–200 mg for depression.
Your doctor starts you at 25 mg (below the target dose).
After one week they increase your dose to 50 mg.
They want to see how you’d do at the low end of the dose range, so they keep you on the 50 mg for four weeks.
After four weeks at 50 mg, how much did your symptoms improve?
Worse? It’s not likely this will be a good medication for you. They’ll drop your dose to 25 mg for a week and then have you stop it and try something else.
Close to 100% improvement? That’s the dose for you, so no need for further increases.
Mostly improved? You’re probably close to the right dose. They’ll increase to 75 mg, wait another four weeks, and evaluate again.
Somewhat improved (i.e., at least 30%)? Odds are the medication will likely help, but you’re not close to the right dose yet. They’ll increase to 75 mg for one week, and then 100 mg. After four weeks at 100 mg, evaluate again.
If 100 mg is very close, they’ll bump it up to 125 mg, wait four weeks, and evaluate that.
Or, if 100 mg is better but still well below 100%, they’ll increase it to 125 mg for one week, then 150 mg, wait four weeks, and evaluate that. They’ll repeat if needed until you reach the maximum 200 mg.
This can vary. For example, say your symptoms are more severe, or you’ve needed doses at the high end of the target range with other antidepressants. Your doctor may increase it weekly by 25 mg until you hit 100 mg or even 150 mg before pausing for several weeks and evaluating. It’s a tradeoff. On the one hand, you may feel better more quickly. On the other hand, you may overshoot the correct dose. You may have too many side effects and need to backtrack.
Knowing whether an antidepressant is helping is trickier than most people think. First, the effect builds up slowly, usually over several weeks at a given dose. Second, it may be difficult to notice your improvement or to quantify the gains you’ve made. Gradual changes are harder to describe than sudden ones. On top of all that, you may have difficulty recalling how you used to feel. This can be caused by your illness itself.
Periodically repeating self-report scales (or using mood tracking apps) may help. They allow you to rate your symptoms over the last week and then compare with previous times you used the scale. Keeping your eye on two or three symptoms that you find particularly bothersome is a more personalized variation. Journalling your symptoms is another approach. Asking family members or others who have spent ample time with you is particularly useful. They usually see changes before you do and can better describe the before and after differences.
Finally, some symptoms tend to improve before others. Problems with fatigue, sleep, and appetite usually improve first. A change in your mood follows. Cognitive and memory deficits can take two or three times as long.
If you’re taking an antidepressant to help with anxiety, you may need a higher dose of medication than used to treat depression. It may also take considerably longer before you notice an improvement in your symptoms.
The usual goal of treatment is to remove all symptoms, whether by medication alone or a combination of interventions. This lets you heal and increases your resilience. If symptoms are only partially treated, you’ll still be constantly fighting your illness. That makes it more likely you’ll experience a recurrence of all your symptoms if you try to stop your treatment. That, in turn, can result in your illness returning full force, and you, ultimately, experiencing another episode with a decline in function and well-being.
One fear that many people have is that antidepressants fundamentally change who they are as a person. Rest assured, this does not happen.
You may find yourself less prone to dark thoughts, or, when they occur, find it easier to get your mind off them. You may no longer have a panic attack when entering a crowded room. You may still be anxious, but not so anxious that you’re overwhelmed and can’t think. Medications can help take the edge off or make it easier for you to break free from an emotional spiral. They do not change your beliefs, your values, your personality, or anything else that makes you you.
While on some medications, you might find that you don’t feel as sad, happy, or excited as you were before you were sick. This is known as emotional numbing. You may find it harder to think through certain problems than in the past, i.e., brain fog. These are side effects and should be identified and managed working with your doctor.
As with all medications, you may experience side effects when taking an antidepressant. The neurotransmitters that regulate your mood control many other systems throughout your body. Side effects are caused by antidepressants affecting neurotransmitters and receptors in all those areas. Some people have no side effects, some have one or two mild effects for a couple of days, and others have severe side effects that don’t go away. Some side effects worsen with higher medication doses. The chance that you will experience a specific side effect differs with each antidepressant. As well, the side effects you experience may be very different than those experienced by a friend on the same medication. It’s not easy to predict.
Side effects can include headache, nausea, dizziness, sweating, itching, tremors, brain fog, poor memory, word-finding difficulties, change in sleep patterns, agitation, constipation, diarrhea, decreased libido, or sexual dysfunction. There are others as well. But, just because a medication may cause a side effect doesn’t mean that you will experience it.
Timing is very important. Side effects primarily occur when first starting a medication and in the few days after the dose increases. Most ease up and disappear after a few days, occasionally lasting up to a few weeks. If they last any longer than that, they’re more likely to persist as long as you’re taking that medication.
Stopping an antidepressant when first experiencing a troublesome side effect is one of the most frequent missteps people make. If you are anxious about taking medication, you may focus on a mild side effect that you otherwise could easily tolerate. Be prepared. Try to start your medication when you don’t need to be at your best for a few days. Don’t overreact. Learn which side effects need to be acted on quickly. For others, try to stick it out a bit. Most of the time, waiting is the answer.
We’ll discuss how to deal with many specific side effects in a later chapter. There will also be information about identifying which side effects need urgent attention and which are annoying but harmless.
Unless you’re on a tiny dose, don’t stop antidepressants cold turkey. Just like starting them, decreasing or stopping needs to be done slowly and in small steps. Otherwise, you’re very likely to experience withdrawal symptoms, not unlike the side effects we described previously.
Some antidepressants have worse withdrawal symptoms than others. A few, such as venlafaxine (Effexor) and paroxetine (Paxil), leave your system quickly when stopped. Many people experience severe withdrawal with them and even notice if they’re a few hours late taking a pill. Others, such as fluoxetine (Prozac), leave your system gradually, minimizing withdrawal. In fact, fluoxetine is often added to smooth out the withdrawal symptoms when stopping other antidepressants. A medication’s half-life is a measure of how quickly it leaves your system. Most antidepressants stay in your system for around two weeks, though fluoxetine stays for around seven weeks.
We said the goal of antidepressant treatment is to resolve all symptoms. Then what? If you’re taking it for depression, current guidelines1 suggest after a first episode you should remain on the medication, at the dose leading to wellness, for at least six to nine months after symptoms have fully resolved. For those with more risk factors, such as having had more than one depressive episode or having a chronic physical illness, at least two years is recommended. For those at high risk, having had multiple, severe episodes, an even greater period is probably wise. Discuss when to stop your medication with your doctor. We recommend it be done at an optimal time of year (many people find their mood is best in summer) and during a period of minimal personal stress (no significant life changes about to occur). Some people remain on medication long term. Discuss the benefits and risks of this with your doctor.
If you’ve glanced at the list of individual antidepressants in Appendix C, you know there are many to choose from. That list covers only the most common ones. Around one third of patients find success on the first one they try. We’ve already said that finding the right one will involve some aspect of trial and error. But this is far from a random process. Many factors can help select the medications most likely to work.
The first thing to consider is: have you taken an antidepressant before, especially in a similar situation, and found it helpful? Trying that same medication or a very similar one would be a good bet. Similar medications may work on the same neurotransmitters and receptors. They can even be patent extenders. These are slightly tweaked versions of a medication released as a new product. They often come with improved side effect profiles.
Mental illness has a strong genetic component to it. If you’ve had close biological family members who’ve taken medications, try to find out which ones. Other things being equal, if a family member had success with a medication, you’re also likely to.
Next, consider your specific symptoms. Different symptoms are correlated with specific neurotransmitters (5-HT, NE, DA). See Table 4.
Let’s see how you or your doctor might use this information:
Your main symptom is a depressed mood. Looking at the table, that can be affected by any of 5-HT, NE, DA, or a combination. That doesn’t give you much information about what antidepressant to try.
If your main symptoms are low motivation and fatigue, a purely serotonergic antidepressant would not be an ideal first choice.
If you suffer from apathy, poor memory, and weight changes, you’ll likely need an antidepressant that targets all three neurotransmitters.
In practice, it’s a lot more complicated. There are many more symptoms, such as anxiety and pain, that are affected by these same neurotransmitters. Let’s add anxiety and ADHD-like symptoms into the mix, as in Table 5.
This tells us a few things:
Antidepressants that increase 5-HT activity improve anxiety. They should be the first choice if your primary symptom is anxiety.
Increased NE activity helps with some depressive symptoms. It can also make anxiety worse but help attention and concentration. With help from your doctor, you may find the right dose of an antidepressant that gives you the best balance between 5-HT and NE.
More DA activity also worsens anxiety. Unfortunately, stimulants used for ADHD primarily increase DA. Those with anxiety and ADHD need to balance medications to manage all their symptoms.
Antidepressants that work on NE and DA (e.g., bupropion) can increase anxiety. If you’re already anxious, they’re more likely to make this worse, not better.
Family doctors who use few antidepressants, and do so less frequently, often don’t thoroughly consider symptom mapping. Psychiatrists may do symptom mapping intuitively. Going through the exercise of explicitly identifying which neurotransmitters your symptoms are affected by may serve as an extra check on medication choice. If you find discrepancies, don’t jump to conclusions about your medication, but discuss them with your doctor.
An antidepressant’s main job is to work on depression or anxiety, and each one uses different neurotransmitters and receptors to do that. Because those are found throughout the body, each antidepressant also affects other systems. When those effects are troublesome, you call them side effects. But sometimes these secondary actions can be put to good use.
You can take advantage of secondary actions to help with not only your mood but also another physical problem. For example, some antidepressants (e.g., nortriptyline, duloxetine) are effective at treating some nerve pain. The antidepressant bupropion is effective at smoking cessation (the company that makes the brand-name version, Wellbutrin, also markets the same medication as Zyban for quitting smoking). Some antidepressants, e.g., trazodone, are very sedating, so can be effective in treating insomnia. Others, e.g., mirtazapine, can lead to increased appetite and weight gain and decreased nausea. That is not usually a good thing, but excellent if depression or another illness has resulted in low appetite, nausea, and weight loss.
Another factor to consider is how your body absorbs medications. Most are first broken down into small pieces in the gastrointestinal system. The liver then metabolizes them into the form the nervous system needs. It does so using a related set of enzymes, which assist with chemical reactions. There are a dozen different enzymes commonly involved, and most antidepressants use one or more. If an enzyme needed by a medication isn’t working well, less will be absorbed by your system, and it will be less effective. These enzymes also transform medications into waste products so they can be removed from the body. Problems can lead to a buildup of medication in your system or a too rapid removal, so it doesn’t have time to work.
These enzymes are a common source of medication interactions. If two medications use the same enzyme, an increase or decrease in the amount of either medication in your system can result. This can be dangerous. The same enzymes are affected by many illicit drugs, herbal supplements, and even some foods, such as grapefruit juice.
There are many other reasons medications shouldn’t be used together or shouldn’t be used if you have some medical conditions. Even future medical issues may need to be taken into account. Thinking of getting pregnant? Some antidepressants are associated with birth defects, while others have been studied extensively and found to be very safe in pregnancy.
Both your doctor and your pharmacist should keep an eye out for dangerous medication interactions. It’s vital that they know everything you’re taking, both prescription medications and herbal supplements.
There are interaction checkers on consumer-oriented websites such as rxlist.com and drugs.com. You type in a list of medications, and the site provides a list of possible interactions. These need to be interpreted by your doctor, who would consider your specific health situation, doses of each medication, and more. A particular interaction may or may not apply to you.
Considering interactions doesn’t stop once you’ve chosen an antidepressant. They may be a factor with any medications you add in future.
The liver enzymes described above are part of a class known as cytochrome P450, and the reactions they assist are called cytochrome P450 pathways. To find out which metabolize a medication or supplement, do an internet search for “CYP450” plus the name of the product.
Interestingly, scientists have found several gene mutations that reduce how well particular pathways work. Ethnic background also affects cytochrome metabolism. Some people already use data from consumer genetics testing, e.g., 23andMe, as a factor in medication selection. For example, they avoid medications absorbed by a pathway if they have the relevant mutations. Expect to see more of this in future.
This section touches on a few more things to be aware of when taking antidepressants. Many are important or serious but will affect very few people.
All antidepressants carry a warning that they may increase the risk of suicidal thinking, feeling, or behaviour in children, adolescents, and, to a lesser degree, adults 18–24, in the initial months of treatment. While the risk is very small, the warning is there due to the severity of the consequences.
Depression itself carries a (much higher) risk of suicidal thoughts and actions. So, what’s going on here? Several factors may be at work. Antidepressants take weeks to work, and symptoms improve at different rates. If you’re depressed and suicidal, you may not have the energy or motivation to act on your thoughts. An antidepressant may boost your energy and motivation long before addressing your thoughts, enabling you to carry out your suicide plan. Second, side effects such as agitation, insomnia, or restlessness can worsen an existing situation. Side effects occur long before the medication has any positive impact. Finally, antidepressants can push people prone to bipolar into a manic state, which carries a higher risk of suicide.
These very small risks can be decreased by thorough history taking and smart prescribing practices. Close monitoring (by you, your doctor, and friend or family supports) is advised when starting any new medication.
Thoughts of suicide are a common symptom of many mental illnesses. They may come and go, and their intensity may vary. Just like other symptoms, don’t hesitate to talk with your care providers about these thoughts. Don’t be afraid that you’ll be locked up just for mentioning it.
It’s common to need small dose adjustments of an antidepressant over time. They could come from more or less stress in your life, or changes in physical health, diet, exercise, or other medications. Sometimes though, you might be on a medication for a few years. With no other changes that you’re aware of, the effectiveness of the antidepressant may decrease.
You might question why your mood has changed so drastically when nothing else has. Often, you and your doctor can find something that’s changed, e.g., via blood work. If not, it may be that your medication has stopped working for you. You may need to increase your dose, or less commonly, start a different antidepressant to replace it.
Most people don’t want to stay on a medication any longer than they need to. Sometimes people stop to see how they feel without it, taking a so-called medication holiday. There is a small chance that if you stop an antidepressant and then later start again, it won’t work as well as it did previously.
Most antidepressants boost serotonin transmission. Too much of a boost can lead to a potentially dangerous condition called serotonin syndrome.2 It very rarely results from taking two or more serotonergic medications (or much higher than the maximum dose of one). If you are taking a serotonergic antidepressant, be aware that many medications, over-the-counter and natural supplements, and illicit drugs also boost serotonin (see Table 6).
Symptoms commonly occur within 24 hours of starting a new serotonergic medication or increasing the dose of one you’re taking. They can include confusion, agitation, sweating, pupil dilation, headache, involuntary twitching, tremor, palpitations, fever, nausea or vomiting, bruising, hypervigilance, pressured speech, and muscle rigidity. While some of these overlap the side effects that can occur when starting or changing doses of some medications, if you experience several of them (all starting within 24 hours of a new medication or dose increase), seek medical advice. Serotonin syndrome can be very serious if left untreated.
Serotonin syndrome should be confirmed by a doctor, as other conditions have similar symptoms. It’s under diagnosed, as there’s no single test to detect it. Doctors should be suspicious of telltale signs such as hyperreflexia, autonomic instability, and decreased platelets.
Be upfront about all medications, supplements, and substances, legal and otherwise, you’ve taken over the last couple of weeks. That includes when you took them, dose changes, and when your symptoms started.3
We talked previously about how alcohol, caffeine, tobacco, and cannabis can affect mental health. People taking antidepressants or other medications often ask if they can drink alcohol with their medication.
The official (or cautious) answer is that you shouldn’t. Alcohol is a depressant and may worsen medication side effects. Alcohol may affect you differently when you’re on the medication than before you started it. It may also change the effect of the medication. Quite frankly, the interaction between alcohol and most medications has not been studied in any great detail.
Despite this, you may plan to drink alcohol. If so, try a small amount in a safe environment. Don’t drive or operate heavy machinery. Consider decreasing the amount of alcohol and limiting it to special occasions. Realize that, even then, it may counteract the effects of your medication.
Antidepressants are complex. Careful selection, start up, monitoring, and adjustment is needed. Patient education can set expectations but is often neglected.
Antidepressants are used for depression, anxiety, many other mental illnesses, and even a few physical illnesses. They are used very carefully, if at all, in people with bipolar disorders, as they can trigger an episode of hypomania or mania.
Antidepressants may take weeks to work. Finding the right dose and dealing with side effects when you start them can take time and some expertise. Stopping them needs to be done gradually to prevent withdrawal.
Choosing an antidepressant is complicated. Genetics play a role. Your symptoms are associated with different neurotransmitters, which can help. Metabolism, medication interactions, and secondary effects also factor in.
Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, et al. “Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological Treatments.” Canadian Journal of Psychiatry. 2016;61(9):540-560.
https://doi.org/10.1177/0706743716659417↩
Volpi-Abadie J, Kaye AM, Kaye AD. “Serotonin syndrome”. The Ochsner Journal. 2013;13(4):533–40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/↩
Except for overdose, serotonin syndrome is virtually always a result of combining two or more serotonergic medications or nutraceuticals. Yet, some medications remain in the body for days or weeks after they’ve been stopped (e.g. fluoxetine). While you may be on only one serotonergic medication now, make sure doctors know if you’ve recently stopped another.
Serotonin syndrome can also be brought on by adding medications or nutraceuticals that aren’t themselves serotonergic! As we mentioned previously, some medications affect the liver pathways that break down medications and remove them from your system. That could result in toxic levels of a serotonergic medication, which could lead to serotonin syndrome. However, serotonin syndrome is very rare.↩
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Now Available! A MSP-supported live course for BC residents based on the book.
