Which Antidepressant is 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. 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, mostly non-sedating and are safe in children, the elderly, and after medical illnesses such as heart attacks. Some SSRIs are commonly used in pregnancy and breastfeeding.

2. 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.

4. Ketamine and Spravato (esketamine): Intravenous infusions of ketamine or esketamine (Spravato) nasal spray are newer treatments. These work faster than regular antidepressants so that's a game-changer. They are helpful for treatment-resistant depression (TRD) and suicidal thoughts. Spravato can only be given at an authorized psychiatric centre and my clinic is one such centre.

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’s also used for ADHD and smoking cessation. People who drink alcohol should be careful because both bupropion and alcohol increase the risk of seizures, albeit rarely.

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 pursuing a healthy, life are 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.

Dr Tomer T. Levin MD is a double board-certified psychiatrist. He was an Associate Professor at the Weill Cornell Medical College before leaving to establish his own centre. His offices are centrally located One Penn Plaza office in NYC and in Great Neck on Long Island.