Best Antidepressants (2023): Top Medications for Depression (Efficacy & Tolerability)

In 2020, it was estimated that ~9.2% of Americans (around 1 in 10) aged 12+ experienced a major depressive episode within the past year (most common in 18-25 year olds at 17.2% followed by adolescents at 16.9%). (R)

Some people effectively manage depression with a combination of behavior & lifestyle modifications (e.g. healthy diet; circadian optimization; regular exercise; quality relationships; stress reduction; sunlight) – but for others, these have no significant impact on mood.

A check up with a medical doctor is recommended and should include: a physical; blood work (CBC, TSH, B12, RPR, HIV, BUN, creatinine, LFT, alcohol level, toxicology, ABG, dexamethasone suppression test, ACTH stimulation, electrolytes, etc.); and possibly brain scans (if certain conditions are suspected). (R)

What can you do if you’re really depressed but nothing seems to be working? Most people try cognitive behavioral therapy (CBT) or some sort of therapy – and in many cases, medication (at least temporarily to get their mood back on track).

Best Antidepressants: Top Medications for Depression (2023)

For this article, I sought to investigate the efficacy & tolerability of antidepressants and determine whether certain medications may be better than others.

There is significant variation in response to antidepressants in terms of efficacy and tolerability – so don’t automatically assume that meds ranked best are the best for everyone.

I wanted to compile what might be the best antidepressants to try based on information taken from multiple sources: (A) User Ratings (adjusted); (B) UpToDate; and (C) Systematic Review for adults; (D) Systematic Review for pediatrics (children & adolescents).

If considering all these sources together, which are the best antidepressants based on a combination of: adjusted user ratings; UpToDate recommendations; and recent reviews?

  • Escitalopram (Lexapro) (A, B, C)
  • Bupropion (Wellbutrin) (A, B, C)
  • Amitriptyline (A, B, C)
  • Fluoxetine (B, D)

According to user ratings, Nefazodone (Serzone) may be one of the most effective antidepressants, however, it can cause liver injury for some – so it’s not as commonly prescribed.

Considering all of the data: Escitalopram (Lexapro); Bupropion (Wellbutrin); and Amitriptyline seem to be some of the better interventions for adults with depression.

Fluoxetine (either alone or with therapy) seems to be the best intervention for pediatrics (children & adolescents) – based on a 2022 systematic review.

Best Antidepressants (Adjusted User Ratings)

Included below are the adjusted average rankings of antidepressants based on publicly-available user ratings from – only for medications with at least 50+ reviews.

The ratings are sorted below from highest adjusted-average ranking to lowest adjusted-average ranking.

High Ratings (7-9)

  1. Tramadol (Off-label) | Rating: 9.2 | Reviews: 204 | Weighted Average: 8.77
  2. Nefazodone | Rating: 9.4 | Reviews: 77 | Weighted Average: 8.14
  3. Alprazolam (Off-label) | Rating: 8.7 | Reviews: 102 | Weighted Average: 7.93
  4. Phenelzine | Rating: 8.5 | Reviews: 134 | Weighted Average: 7.91
  5. Parnate | Rating: 8.5 | Reviews: 91 | Weighted Average: 7.66
  6. Tranylcypromine | Rating: 8.3 | Reviews: 111 | Weighted Average: 7.61
  7. Modafinil (Off-label) | Rating: 8.7 | Reviews: 69 | Weighted Average: 7.59
  8. Nardil | Rating: 8.3 | Reviews: 106 | Weighted Average: 7.58
  9. Methylphenidate | Rating: 8.7 | Reviews: 64 | Weighted Average: 7.52
  10. Amitriptyline | Rating: 8.0 | Reviews: 133 | Weighted Average: 7.44
  11. Niacin (Off-label) | Rating: 8.7 | Reviews: 56 | Weighted Average: 7.38
  12. Wellbutrin XL | Rating: 7.4 | Reviews: 305 | Weighted Average: 7.16
  13. Citalopram | Rating: 7.2 | Reviews: 718 | Weighted Average: 7.10
  14. Lexapro | Rating: 7.2 | Reviews: 613 | Weighted Average: 7.08
  15. L-Methylfolate | Rating: 7.6 | Reviews: 136 | Weighted Average: 7.07
  16. Escitalopram | Rating: 7.1 | Reviews: 908 | Weighted Average: 7.02
  17. Celexa | Rating: 7.2 | Reviews: 364 | Weighted Average: 7.01

Mid Ratings (5-7)

  • Bupropion | Rating: 7.0 | Reviews: 1356 | Weighted Average: 6.95
  • Prozac | Rating: 7.0 | Reviews: 428 | Weighted Average: 6.84
  • Pristiq | Rating: 6.9 | Reviews: 788 | Weighted Average: 6.81
  • Lamotrigine (Off-label) | Rating: 7.2 | Reviews: 176 | Weighted Average: 6.81
  • Fluoxetine | Rating: 6.9 | Reviews: 710 | Weighted Average: 6.80
  • Sertraline | Rating: 6.8 | Reviews: 1227 | Weighted Average: 6.75
  • Desvenlafaxine | Rating: 6.8 | Reviews: 854 | Weighted Average: 6.72
  • Zoloft | Rating: 6.8 | Reviews: 619 | Weighted Average: 6.69
  • Remeron | Rating: 7.0 | Reviews: 169 | Weighted Average: 6.61
  • Deplin | Rating: 7.3 | Reviews: 92 | Weighted Average: 6.58
  • Mirtazapine | Rating: 6.6 | Reviews: 631 | Weighted Average: 6.50
  • Brexpiprazole | Rating: 6.9 | Reviews: 151 | Weighted Average: 6.47
  • Rexulti | Rating: 6.9 | Reviews: 138 | Weighted Average: 6.43
  • Effexor XR | Rating: 6.5 | Reviews: 356 | Weighted Average: 6.32
  • Paroxetine | Rating: 6.5 | Reviews: 291 | Weighted Average: 6.28
  • Abilify | Rating: 6.4 | Reviews: 326 | Weighted Average: 6.21
  • Wellbutrin SR | Rating: 6.8 | Reviews: 104 | Weighted Average: 6.20
  • Trazodone | Rating: 6.6 | Reviews: 134 | Weighted Average: 6.14
  • Aripiprazole | Rating: 6.3 | Reviews: 355 | Weighted Average: 6.13
  • Cymbalta | Rating: 6.3 | Reviews: 597 | Weighted Average: 6.12
  • Duloxetine | Rating: 6.2 | Reviews: 729 | Weighted Average: 6.11
  • Paxil | Rating: 6.4 | Reviews: 192 | Weighted Average: 6.08
  • Quetiapine | Rating: 6.4 | Reviews: 190 | Weighted Average: 6.08
  • Seroquel XR | Rating: 7.1 | Reviews: 52 | Weighted Average: 5.95
  • Venlafaxine | Rating: 6.0 | Reviews: 1011 | Weighted Average: 5.94
  • Trintellix | Rating: 6.0 | Reviews: 611 | Weighted Average: 5.90
  • Vortioxetine | Rating: 5.9 | Reviews: 897 | Weighted Average: 5.83
  • Vilazodone | Rating: 5.9 | Reviews: 612 | Weighted Average: 5.805
  • Viibryd | Rating: 5.9 | Reviews: 592 | Weighted Average: 5.80
  • Nortriptyline | Rating: 6.3 | Reviews: 63 | Weighted Average: 5.43
  • Effexor | Rating: 5.5 | Reviews: 341 | Weighted Average: 5.34
  • Lithium (Off-label) | Rating: 6.0 | Reviews: 62 | Weighted Average: 5.17

Low ratings (<5)

  • Esketamine | Rating: 5.7 | Reviews: 67 | Weighted Average: 4.96
  • Spravato | Rating: 5.5 | Reviews: 60 | Weighted Average: 4.71
  • Olanzapine | Rating: 4.9 | Reviews: 180 | Weighted Average: 4.64
  • Zyprexa | Rating: 5.1 | Reviews: 83 | Weighted Average: 4.56
  • Levomilnacipran | Rating: 4.9 | Reviews: 102 | Weighted Average: 4.46
  • Risperidone (Off-label) | Rating: 5.1 | Reviews: 55 | Weighted Average: 4.31
  • Fetzima | Rating: 4.7 | Reviews: 91 | Weighted Average: 4.23

I did NOT consolidate brand name with generic out of curiosity – I wanted to see whether there were any significant disparities between a brand name medication and its generic.

Major disparities between a brand name and generic may indicate: (A) marketing manipulation campaign (fake reviews) OR (B) one being superior to the other in efficacy (unlikely but possible).

How was the adjusted average determined?

A formula that accounted for: (A) rating from 1-10 (10 is the highest) & (B) number of user ratings.

The formula was as follows: (Rating * # of Reviews) / (# of Reviews + 10).

This formula factors in sample size while reducing the impact of outliers – and provides a more accurate and fairer representation compared to standard user average.

Best Antidepressants (Average Rankings)

I also created a list of the best antidepressants with at least double-digit reviews – focusing specifically on the unadjusted user rating.

Why? It’s possible that some medications with few reviews are far more effective than the adjusted rating suggests.

  1. Nefazodone: 9.4/10 (77 ratings)
  2. Tramadol: 9.2/10 (204 ratings)
  3. Alprazolam: 8.7/10 (102 ratings)
  4. Methylphenidate: 8.7/10 (64 ratings)
  5. Modafinil: 8.7/10 (69 ratings)
  6. Niacin: 8.7/10 (56 ratings)
  7. Phenelzine (Nardil): 8.57/10 (240 ratings)
  8. Tranylcypromine (Parnate): 8.23/10 (202 ratings)
  9. Amitriptyline: 8/10 (133 ratings)
  10. Selegiline (Emsam): 8/10 (74 ratings)
  11. L-Methylfolate (Deplin): 7.53/10 (228 ratings)
  12. Citalopram (Celexa): 7.2/10 (1082 ratings)
  13. Lamotrigine: 7.2/10 (176 ratings)
  14. Escitalopram (Lexapro): 7.15/10 (1521 ratings)
  15. Seroquel XL: 7.1/10 (52 ratings)
  16. Bupropion (Wellbutrin): 7.07/10 (1661 ratings)
  17. Mirtazapine (Remeron): 7/10 (169 ratings)
  18. Fluoxetine (Prozac): 6.69/10 (1138 ratings)

Other drugs with high ratings for depression included: Desipramine: 9.1/10 (16 ratings); Lisdexamfetamine: 8.6/10 (21 ratings); Armodafinil: 8.3/10 (41 ratings); Ketamine: 7.1/10 (24 ratings); Atomoxetine: 7.1/10 (8 ratings) – but they had <50 ratings so were not included in the list.

Analysis: Adjusted vs. basic average (commonalities)

Tramadol, nefazodone, and alprazolam reign supreme in the top 3 – and only one of these is approved for the treatment of depression.

Phenelzine (Nardil) and Tranylcypromine (Parnate) are the second and third-highest rated medications that are actually approved for the treatment of depression – but they aren’t commonly used because they are MAOIs (monoamine oxidase inhibitors) with higher risk of adverse events.

Modafinil (Provigil) and Methylphenidate (Ritalin & Focalin) are rated highly, but are not formally approved for the treatment of depression.

Amitriptyline is a tricyclic antidepressant that appears effective in user ratings and systematic reviews – in fact it had the highest antidepressant effect of any drug based on odds ratios.

Niacin (Vitamin B3) and L-Methylfolate a.k.a. “Deplin” (Vitamin B9) appear useful for the treatment of depression – and are good natural options to try.

Bupropion (Wellbutrin), an atypical antidepressant, seems to work well for many – and various SSRIs such as: Escitalopram (Lexapro), Citalopram (Celexa), and Fluoxetine (Prozac) seem to be good options too.

What were the worst antidepressants (adjusted vs. basic average)?

The worst antidepressants based on both adjusted and basic average on included:

  1. Levomilnacipran (Fetzima): 4.8/10 (193 ratings)
  2. Esketamine (Spravato): 5.6/10 (127 ratings)
  3. Olanzapine (Zyprexa): 5/10 (163 ratings)
  4. Risperidone (Risperdal): 5.1/10 (55 ratings)
  5. Venlafaxine (Effexor): 5.93/10 (1352 ratings)

Of these medications, Levomilnacipran (Fetzima) and Venlafaxine (Effexor) are approved as first-line interventions.

Esketamine (Spravato) is approved for treatment-resistant depression and antipsychotics like Risperidone (Risperdal) & Olanzapine (Zyprexa) are sometimes prescribed as adjunct treatments in severe cases.

Note: It’s a bit odd that Esketamine (Spravato) was rated so low relative to actual Ketamine. That said, research supports the idea that IV ketamine is superior to intranasal esketamine for depression. (R)

What about long-term efficacy (according to user ratings)?

Every single antidepressant I checked (with a reasonable number of reviews) had a subset of people who used it long-term (2-years, 5-years, 10-years, 15-years, 20-years) with favorable effect.

In other words, some people are able to stay on these medications for a long-term without the need to discontinue due to side effects or a diminishing antidepressant effect or dosage adjustments.

This includes medications like tramadol, modafinil, nefazodone, escitalopram, phenelzine, amitriptyline, etc. – and some plan on taking these drugs for life if possible.

Some long-term users find that the antidepressant efficacy of a medication wanes over time – such that they need to switch to a different drug OR increase the dosage OR discontinue.

Major complaints for long-term users of certain medications included: suspected formula changes (different manufacturer & drug didn’t work as well); withdrawal difficulty; adverse reactions (brain fog, sweating, weight gain, sexual dysfunction, etc.); and medication stopped working (tolerance).

What are the takeaways from user reviews?

The main takeaway is that the antidepressants users seem to rate highest (based on adjusted & non-adjusted ratings) are not commonly prescribed.

Substances with atypical mechanisms of action such as: tramadol, nefazodone, alprazolam, modafinil, methylphenidate, bupropion, etc. – may work well for some cases of depression.

Even vitamins (B3 & B9) in the form of niacin & L-methylfolate seem to have high ratings… and should probably be tried before medications for the sake of safety.

  • Tramadol: An SNRI with an opioidergic effect (MOR agonist).
  • Nefazodone: SSRI & 5-HT2 antagonist.
  • Alprazolam: GABA-A receptor modulator.
  • Stimulants: Modafinil (dopamine, norepinephrine, histamine, orexin); Methylphenidate (dopamine, norepinephrine); Bupropion (NDRI)
  • MAOIs: Phenelzine (non-selective MAOI) & Tranylcypromine (mainly MAO-A)
  • Vitamins: Niacin (neurotransmitter synthesis & reduces inflammation) & L-Methylfolate (neurotransmitter synthesis & HPA modulation)
  • TCA: Amitriptyline (inhibits reuptake of serotonin & norepinephrine)
  • SSRIs: Escitalopram & Citalopram (inhibit reuptake of serotonin)

One advantage of analyzing data is that it accounts for off-label antidepressants which haven’t been formally studied in the treatment of depression – and such they won’t appear in systematic reviews/meta-analyses of efficacy & tolerability.

Limitations with antidepressant ratings…

There are various limitations associated with using data from for antidepressant ratings – including (but not limited to):

  • Sample sizes: Not all medications have a significant number of reviews… Some medications with few reviews may work very well and/or better than those with many reviews – such that the averages from cannot be extrapolated to clinical practice.
  • Confounds: Reviews may conflate efficacy & side effects/adverse reactions – such that some reviews given may be focused more on efficacy OR side effects… others may be a combination of both. Some people may be using multiple psychiatric medications too (making it difficult to know which is having the antidepressant effect.)
  • Fake reviews: It’s possible that a subset of reviews are fake – perhaps intentionally by pharma companies to distort public perception. If more people assume a medication is effective, they may be more likely to request it from their doctor over another.
  • Polarization: Review sites can attract extreme opinions (e.g. worked amazing OR was the worst drug ever). Many people aren’t motivated to leave reviews unless they really love OR hate whatever they’re using.
  • Misreporting: Some reviewers may accidentally falsify information within their review – such as noting that they’ve been using an antidepressant for 5 years when they’ve really only been on it 5 months (could be unintentional too).

Best antidepressants according to medical recommendations & scientific reviews?

I analyzed a combination of scientific & medical sources to determine whether there is one best antidepressant option relative to others.

In adults, medical experts recommend starting treatment with SSRIs/SNRIs – and systematic reviews suggest escitalopram (Lexapro) & sertraline (Zoloft) are good choices. Bupropion (Wellbutrin) seems to be a good choice as well for an atypical intervention.

In children & adolescents, fluoxetine (Prozac) seems to be the most evidence-based intervention.

UpToDate: Depression Treatment Options for Adults (R)

As of 2023, Rush et al. suggest that SSRIs are the recommended first-line intervention for most cases of depression (mild, moderate, severe).

SSRIs: For people with mild-to-moderate depression who wish to use medication. Why? SSRIs offer as much benefit as other meds with the least amount of risk in safety and side effects.

Alternatives to SSRIs include: SNRIs, atypical antidepressants, and serotonin modulators. (SNRIs or mirtazapine may be preferred over SSRIs for severe depression.)

Tricyclic antidepressants and MAOIs aren’t recommended for initial treatment because of side effects and adverse events.

Authors state that all second-gen antidepressants have approximate equal efficacy – so providers can select based on:

  • Medication safety & side effect profile
  • Specific depressive symptoms (subtype)
  • Comorbidities (psychiatric & medical)
  • Other medications used by patient (possible interactions)
  • Medication ease-of-use
  • Patient preference(s)
  • Cost of medications (covered by insurance?)
  • Previous responses to antidepressants (if past depression)

Note: Authors recommend combining antidepressants with psychotherapy – given that studies have showed combination treatment to be more effective than medication alone.

2018: Comparative efficacy & acceptability of 21 antidepressant drugs for acute treatment of adults with major depressive disorder (R)

Cipriani et al. conducted a systematic review & network meta-analysis comparing the effectiveness and tolerability of antidepressants in the treatment of major depressive disorder in adults.

A total of 522 RCTs encompassing 116,477 participants were analyzed for the findings.

Strengths: Comprehensive analysis (one of the most comprehensive to date); network meta-analysis (compared efficacy & tolerability); methodological rigor; transparency; applicability; implications for shared decision-making (may assist in shared decision making when selecting medications).

Limitations: Risk of bias (522 trials = high risk, 380 = moderate risk); evidence certainty (moderate to low); inadequate reporting of randomization & allocation concealment; limited investigation of individual patient factors; exclusion of subgroups (psychosis & treatment-resistant depression); short trial durations; limited adverse event reporting; potential biases & variations in study design; no access to unpublished data.

Important: “All statements comparing the merits of one antidepressant with another must be tempered by the potential limitations of the methodology.”

What were the best antidepressants? (Efficacy & tolerability)

Authors analyzed efficacy based on (A) efficacy (vs. placebo & head-to-head) & (B) tolerability (vs. placebo & head-to-head).

Below are antidepressants that ranked highly in efficacy and tolerability – both in placebo-controlled trials and head-to-head trials.

  • Escitalopram: Ranked highly in both efficacy & tolerability compared to placebo & other antidepressants (head-to-head).
  • Agomelatine: Ranked highly in efficacy and tolerability compared to placebo & other antidepressants (head-to-head).
  • Bupropion: Ranked highly in head-to-head studies of efficacy & tolerability.
  • Sertraline: Ranked highly in tolerability – both in comparison to placebo & head-to-head studies.

What were the worst antidepressants? (Efficacy & tolerability)

Antidepressants with low efficacy and/or poor tolerability are deemed the “worst.”

  • Reboxetine: Ranked least tolerable in head-to-head studies & lowest in efficacy vs. placebo.
  • Clomipramine: Ranked among the least tolerable compared to placebo & compared to other antidepressants – also ranked lower in efficacy.
  • Trazodone: Ranked among the least tolerable & least effective in head-to-head studies. Also ranked fairly low in efficacy vs. placebo.
  • Fluvoxamine: Ranked among least tolerable & least effective in head-to-head studies.
  • Duloxetine: Ranked among the least tolerable in comparison to placebo control.

What were the most effective antidepressants?

If going by placebo-controlled trials AND head-to-head trials, the most effective antidepressants appear to be the following.

  1. Amitriptyline
  2. Escitalopram
  3. Paroxetine
  4. Venlafaxine

What were the least effective antidepressants?

Antidepressants that ranked near the bottom in efficacy vs. placebo and other antidepressants were as follows:

  1. Reboxetine
  2. Fluoxetine

Efficacy (response rate vs. placebo)

All antidepressants were more effective than placebo control – amitriptyline was most effective based on odds ratio.

The odds ratios represent likelihood of improvement with medication compared to placebo and higher odds radios indicate greater efficacy.

  1. Amitriptyline (OR: 2.13)
  2. Mirtazapine (OR: 1.89)
  3. Duloxetine (OR: 1.85)
  4. Venlafaxine (OR: 1.78)
  5. Paroxetine (OR: 1.75)
  6. Milnacipran (OR: 1.74)
  7. Fluvoxamine (OR: 1.69)
  8. Escitalopram (OR: 1.68)
  9. Nefazodone (OR: 1.67)
  10. Sertraline (OR: 1.67)
  11. Vortioxetine (OR: 1.66)
  12. Agomelatine (OR: 1.65)
  13. Vilazodone (OR: 1.60)
  14. Levomilnacipran (OR: 1.59)
  15. Bupropion (OR: 1.58)
  16. Fluoxetine (OR: 1.52)
  17. Citalopram (OR: 1.52)
  18. Trazodone (OR: 1.51)
  19. Clomipramine (OR: 1.49)
  20. Desvenlafaxine (OR: 1.49)
  21. Reboxetine (OR: 1.37)

Efficacy (head-to-head)

In head-to-head studies, the most effective antidepressants (ORs: 1.96 to 1.19) are listed below.

  1. Vortioxetine
  2. Bupropion
  3. Escitalopram
  4. Mirtazapine
  5. Amitriptyline
  6. Agomelatine
  7. Paroxetine
  8. Venlafaxine

Least effective (head-to-head): Fluoxetine, fluvoxamine, reboxetine, trazodone (ORs: 0.51-0.84).

Acceptability (dropout rate vs. placebo)

Below are antidepressants regarded as being the most tolerable relative to placebo control. Agomelatine was most tolerable, followed by fluoxetine, escitalopram, etc.

  1. Agomelatine (OR: 0.84)
  2. Fluoxetine (OR: 0.88)
  3. Escitalopram (OR: 0.90)
  4. Nefazodone (OR: 0.93)
  5. Citalopram (OR: 0.94)
  6. Amitriptyline (OR: 0.95)
  7. Paroxetine (OR: 0.95)
  8. Milnacipran (OR: 0.95)
  9. Sertraline (OR: 0.96)
  10. Bupropion (OR: 0.96)
  11. Mirtazapine (OR: 0.99)

Least tolerable: Clomipramine (worst), levomilnacipran, reboxetine, trazodone, vilazodone, fluvoxamine, duloxetine, desvenlafaxine, venlafaxine, vortioxetine.

Acceptability (head-to-head studies)

The most tolerable antidepressants in head-to-head studies were as follows (with ORs: 0.43-0.77).

  1. Vortioxetine
  2. Agomelatine
  3. Escitalopram
  4. Citalopram
  5. Sertraline
  6. Fluoxetine

Least tolerable (head-to-head): Reboxetine (worst), clomipramine, duloxetine, fluvoxamine, trazodone, nefazodone, amitriptyline.

2020: Comparative efficacy & acceptability of antidepressants in children & adolescents (R)

Zhou et al. conducted a systematic review & meta-analysis comparing the effectiveness and tolerability of antidepressants in the treatment of depressive disorders among children & adolescents.

A total of 71 RCTs encompassing 9,510 participants randomly assigned to 28 active interventions or 4 control conditions – were analyzed for the findings.

What were the most effective antidepressants?

Only fluoxetine plus CBT and fluoxetine (standalone) were more effective than pill placebo in children & adolescents with depressive disorders.

  • Fluoxetine (standalone)
  • Fluoxetine + CBT (Cognitive Behavioral Therapy)

Interpersonal psychotherapy was more effective than all psychological controls – but with very low confidence of evidence.

Interestingly, fluoxetine (along with nefazodone) was also among the best tolerated medications (fewer dropouts than sertraline, imipramine, and desipramine).

Some medications like nortriptyline were worse than most active controls in treating depression in children & adolescents.

Venlafaxine (Effexor) was associated with a significantly increased suicidal behavior/ideation relative to pill placebo and 10 other interventions.

Strengths: The most comprehensive analysis of available evidence to date.

Limitations: Low quality comparisons (inadequate reporting & difficulty using double-blind design for therapy); inconsistent efficacy outcomes (due to changes in design & variations in measurement scales); exclusion of certain patient subgroups (treatment-resistant depression); potential bias (from selective reporting); uncertainty regarding accuracy of data (from certain trials); potential dose effects & variation in half-lives; limited information on certain outcomes (adverse events, discontinuation, global functioning, etc.); limited network meta-analysis (small number of trials comparing same treatments).

Effects of antidepressants may vary between individuals – so patients, caregivers, and clinicians should carefully balance the risk-benefit profile of: efficacy, tolerability, and suicide risk associated with interventions for young patients on a case-by-case basis.

Strategies for dealing with depression…

Below are my thoughts on dealing with depression… if you’re depressed – seek medical attention and address it as soon as possible.

First: Have a medical doctor out preexisting conditions that may be causing the depression.

1. Environment: Analyze your environment. Take steps to improve it if possible. (Natural light, greenery, noise reduction, neighborhood, etc.) – whatever things put you in a better mood.

2. Social support: If possible avoid people that you clash with who cause a lot of stress & negatively affect mood. Spend time with those who positively affect mood.

3. Lifestyle: Focus on the basics. Exercise. Nutritious diet. Proper sleep/wake times. Stress reduction. Self-care. Time management. Work routine. Healthy hobbies.

4. Supplements: There are a variety of supplements that may help with depression – but mileage may vary.

Always confirm safety with a medical doctor and/or pharmacist before testing any supplements.

Note: Links are affiliate links. Price is the same either way – sometimes lower. Buying through my link helps support my work. Appreciated if you do.

There are a variety of other supplements that can be tested but I’m not going to list everything in this article. (R)

Credit to Thurfah et al. (2022) for the recent literature review of dietary supplements for the treatment of depression. (R)

5. Therapy: Psychotherapy is routinely recommended as a nonpharmacological intervention for depression – it may work well for some.

6. Medications: Medications are probably a good option for severe cases of depression – but may not be ideal over a long-term for a variety of reasons.

  • Standard options: Most medical doctors will prescribe SSRIs/SNRIs first – and select based on patient preferences, other medication use, comorbidities, etc.
  • Atypical options: If first-line options fail, atypical options may be tested (e.g. bupropion, amitriptyline, phenelzine, nefazodone, etc.).
  • Adjunct options: Some doctors may prescribe adjunct interventions to address specific aspects of depression like: (A) energy, motivation, etc.: modafinil/armodafinil, methylphenidate, lisdexamfetamine, atomoxetine, etc. OR (B) stress, anxiety, etc.: alprazolam OR (C) pain: tramadol, gabapentin, etc.
  • Last resort: Neurostimulation (TMS, Deep Brain Stimulation; Vagus Nerve Stimulation); Ketamine; Psilocybin; COX-2 inhibitors; ECT; Seizure Therapy; Sleep Deprivation; Whole-Body Heating; MDMA-assisted therapy; etc.

Have you tried any antidepressants?

Did the antidepressants you tried actually help with your depression?

Which specific antidepressants did you try? Which were most effective & least effective?

Which was the best medication you’ve used?

How long did you take an antidepressant? Did it work well the entire time? Any adverse reactions OR unwanted long-term effects?

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