The Depression and Anxiety Experts

What Antidepressants are Best?

Choosing the right antidepressant is important. There are a vast array of antidepressants and knowing where to start can be confusing.

Here are five ways that I, as a psychiatrist, think about choosing an antidepressant:

  1. SSRIs: Selective Serotonin Re-uptake Inhibitors (SSRIs), were revolutionary when they were introduced in the 1980s and have been so successful that their names are familiar to most. Examples are fluoxetine (Prozac), sertraline (Zoloft) and escitalopram (Lexapro). SSRIs are well tolerated, weight neutral and mostly non-sedating. They are considered to be safe in children, the elderly, after medical illnesses such as heart attacks and in overdose. Some SSRIs are commonly used in pregnancy and breastfeeding. Certain people may have a genetic variant that makes them less likely to respond to this group of medications.
  2. SNRIs: Serotonin Norepinephrine Re-Uptake Inhibitors (SNRIs) were the next generation of antidepressants after SSRIs. They work via serotonin and norepinephrine so they have a dual mechanism of action. Examples are venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta)  and milnacipran (Savella). I like the dual mechanism of action because the depression pathway involves numerous neurotransmitters, not just serotonin. I also like that SNRIs can help pain symptoms, especially nerve pain and the aches and pains of depression and fibromyalgia, which the SSRIs typically don’t. Side-effects are similar to the SSRIs above.
  3. Sedating Antidepressants: These include mirtazapine, trazodone and doxepin. For many patients with depression, improving sleep is a priority and these medications can really help insomnia from the get-go because they are sedating. Trazodone is commonly prescribed by primary care doctors who don’t want to prescribe a controlled medication like a benzodiazepine for insomnia. Mirtazapine (Remeron) can stimulate the appetite so that that’s helpful for people who have lost weight from being depressed but less helpful if you don’t want to gain weight. Doxepin is an older antidepressant that also works well to improve sleep.
  4. Ketamine and Esketamine: Intravenous infusions of ketamine or esketamine (Spravato) nasal spray are newer treatments. These work faster than regular antidepressants so that’s helpful with patients who are suicidal. They are also useful for treatment resistant depression (TRD). TRD is where a person has not responded adequately to previous antidepressants. They are only given in a doctor’s office because blood pressure needs to be monitored. Each treatment takes about 2 hours, two to three times/week for two weeks so that can be challenging for patients who work. On the plus side, within one to two weeks, you should know whether the medication helps or not, whereas with SSRIs and SNRIs, it could be 3-12 weeks until you reach maximum dose.
  5. Anti-depressants without sexual side-effects: In some people, SNRIs and SSRIs can impact libido, erection and orgasm and, while there are workarounds, it can be troublesome.  Uniquely, bupropion (Wellbutrin) works via dopamine and has no sexual side effects. It is also stimulating so it can help with concentration or ADHD but, occasionally, because it’s activating, it can make some people feel more anxious. It’s also used for smoking cessation, so if you are a depressed smoker, this medication is a two-for-one. The most serious side effect of bupropion is that it can rarely increase the risk of seizures. People who drink alcohol should be careful because alcohol also increases the risk so it can have an additive effect.

My general rule is to start an antidepressant slowly, taking half a tablet for a few days to see if it suits you. A wave of nausea, if it occurs, is transient. I like seeing my patients one week after starting an antidepressant to make sure there are no side-effects, to assess for suicidal thoughts and to encourage hope.

At my psychiatry center, I re-assess the response to the antidepressant every one to three weeks. If the response is inadequate, I cautiously increase the dose.

Antidepressants are an amazing tool and, in my opinion, one of the greatest inventions of the 20th century. It’s not, however, all about medications.

Targeting the triggers for depression, addressing loss, improving work and relationships and reducing alcohol and cannabis use are helpful too. Pursuing a healthy, meaningful and engaged life is also vital.

Depression may actually be an opportunity to rethink and grow. Seeing depression from this perspective is easier said than done but meaningful change can be liberating. The right anti-depressant can be the first step along a new pathway of hope.

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