As of 2019, approximately 301 million people globally were living with an anxiety disorder (including 58 million pediatrics) – making them the most common mental health problem. (R)
Anxiety disorders are thought to be caused by a combination of environmental variables (social, activity level, diet, stressors, medication/substance use, trauma, etc.) interacting with genetic predisposition (low vs. moderate vs. high).
Some people are able to manage anxiety with lifestyle modifications such as: stress management; mindfulness; meditation; sleep prioritization; stimulant cessation/reduction; regular exercise; quality relationships – but these won’t work for everyone.
Medical evaluation is recommended to rule out and/or treat obvious causes of anxiety. This should include: full physical; blood work (hormones, vitamins/nutrients/electrolytes, toxicology, etc.); and possibly brain scans (if certain conditions are suspected by the doctor).
If lifestyle modifications aren’t working well and nothing causative is pinpointed in medical evaluations, using an a medication approved for the treatment of anxiety may be helpful – (at least temporarily to get stress under control).
Best Anxiety Medications: Top Anxiolytic Drugs (2023)
I attempted to determine the best anxiety medications (efficacy & tolerability) based on a combination of: (A) user ratings (adjusted); (B) medical recommendations; (C) recent systematic reviews & meta-analyses.
Why consider user ratings? Because many medications reviewed by users are not approved to treat anxiety and a subset of reviews have been made by users that take these medications for much longer-terms than in clinical trials.
Understand that there is significant intra-individual variation in anxiolytic response & tolerability to medications – so don’t assume that the highest ranked medications are universally better for everyone.
Considering all sources, which medications are best for the treatment of anxiety in adults?
- Escitalopram (A, B, C): First-line option. Highest ranking SSRI from user reviews.
- Paroxetine (A, B, C): First-line option. Second-highest ranking SSRI from user reviews.
- Venlafaxine XR (A, B, C): First-line or second-line option. Reasonable user reviews.
- Gabapentin & Pregabalin (A, B, C): Second-line or third-line options. Rank better than SSRIs in user reviews. Effective & well-tolerated in trials.
- Sertraline (B, C): First-line option. Among the most tolerable options. No user reviews.
- Agomelatine (C): Among the most effective & tolerable options in systematic reviews. Not a first-line option due to risk of liver injury (ALI).
- Alprazolam (A): Most effective benzodiazepine by user reviews. Well-tolerated in studies.
- Tramadol (A): Most effective treatment for anxiety by adjusted & unadjusted user reviews. Not formally studied.
Benzodiazepines (e.g. alprazolam, clonazepam, diazepam, lorazepam) are probably the most effective short-term/acute treatment for acute anxiety episodes but aren’t recommended for long-term use (7 of the top 10 ranked meds for anxiety by users were benzos).
What about in pediatrics (children & adolescents)?
SSRIs & psychotherapy appear to be the best options for anxiety in pediatrics – sertraline, paroxetine, guanfacine, and fluvoxamine may be among the best medication choices (based on efficacy/tolerability from a 2019 review).
Considering a combination of user reviews, systematic reviews, and medical recommendations – the worst medications for anxiety are probably:
- Buspar (buspirone): Subpar efficacy & user ratings (5.8/10).
- Prochlorperazine: Lowest user ratings (1.9/10).
- Tiagabine: Poor efficacy in systematic reviews.
- Vortioxetine: Poor efficacy in systematic reviews.
- Antipsychotics: Poor user reviews & high risk of adverse events (e.g. metabolic syndrome).
Nonpharmacological interventions that have poor efficacy for anxiety disorders include: IPT (interpersonal therapy); EMDR; non-face-to-face therapies; psychodynamic therapy; and relaxation.
- Related article: Best Antidepressants (2023)
Top 9 Anxiety Medications (Adjusted User Ratings)
Included below are anxiety medications ranked based on adjusted user reviews.
I only included medications with at least 50 reviews in the rankings and didn’t consolidate brand name with generic – mostly because I wanted to see if they differed in rank.
Most brand name and generic medications ranked similarly – which should be expected (alprazolam/Xanax, Ativan/lorazepam, Lexapro/escitalopram, Paxil/paroxetine, venlafaxine/Effexor, duloxetine/Cymbalta, Buspar/buspirone, etc.).
- Tramadol: Rating: 9.3 | Reviews: 107 | Weighted Average: 8.51
- Alprazolam: Rating: 8.6 | Reviews: 844 | Weighted Average: 8.5
- Clonazepam: Rating: 8.5 | Reviews: 782 | Weighted Average: 8.4
- Xanax: Rating: 8.5 | Reviews: 555 | Weighted Average: 8.35
- Valium: Rating: 8.7 | Reviews: 198 | Weighted Average: 8.3
- Diazepam: Rating: 8.4 | Reviews: 468 | Weighted Average: 8.22
- Lorazepam: Rating: 8.0 | Reviews: 663 | Weighted Average: 7.9
- Ativan: Rating: 8.1 | Reviews: 336 | Weighted Average: 7.9
- Gabapentin: Rating: 7.9 | Reviews: 452 | Weighted Average: 7.73
- Lexapro: Rating: 7.5 | Reviews: 912 | Weighted Average: 7.42
- Escitalopram: Rating: 7.4 | Reviews: 1494 | Weighted Average: 7.35
- Propranolol: Rating: 7.4 | Reviews: 362 | Weighted Average: 7.2
- Oxazepam: Rating: 8.4 | Reviews: 56 | Weighted Average: 7.12
- Paxil: Rating: 7.2 | Reviews: 266 | Weighted Average: 6.94
- Paroxetine: Rating: 7.1 | Reviews: 369 | Weighted Average: 6.91
- Desvenlafaxine: Rating: 7.2 | Reviews: 185 | Weighted Average: 6.83
- Effexor XR: Rating: 7.0 | Reviews: 236 | Weighted Average: 6.72
- Atenolol: Rating: 7.9 | Reviews: 52 | Weighted Average: 6.63
- Mirtazapine: Rating: 6.6 | Reviews: 512 | Weighted Average: 6.5
- Lamotrigine: Rating: 7.0 | Reviews: 109 | Weighted Average: 6.41
- Venlafaxine: Rating: 6.5 | Reviews: 408 | Weighted Average: 6.34
- Cymbalta: Rating: 6.4 | Reviews: 298 | Weighted Average: 6.2
- Clonidine: Rating: 6.9 | Reviews: 86 | Weighted Average: 6.2
- Trazodone: Rating: 6.5 | Reviews: 131 | Weighted Average: 6.04
- Duloxetine: Rating: 6.2 | Reviews: 388 | Weighted Average: 6.04
- BuSpar: Rating: 5.9 | Reviews: 531 | Weighted Average: 5.8
- Buspirone: Rating: 5.8 | Reviews: 1063 | Weighted Average: 5.75
- Bupropion: Rating: 5.9 | Reviews: 175 | Weighted Average: 5.6
- Hydroxyzine: Rating: 5.5 | Reviews: 876 | Weighted Average: 5.44
- Vilazodone: Rating: 6.1 | Reviews: 66 | Weighted Average: 5.3
- Vistaril: Rating: 5.4 | Reviews: 192 | Weighted Average: 5.13
- Risperidone: Rating: 4.8 | Reviews: 69 | Weighted Average: 4.2
- Prochlorperazine: Rating: 2.1 | Reviews: 87 | Weighted Average: 1.9
Note: It’s possible that there were errors in data extraction/calculations.
How were the adjusted average rankings determined?
Formula: (Rating * # of Reviews) / (# of Reviews + 10)
This formula accounts for: (A) Rating (1-10 scale) & (B) # of Reviews – giving more weight to medications with a greater number of reviews and slightly less weight to those with fewer.
The thought is that the weighted or adjusted averages above will be more accurate & fairer in terms of representation relative to the basic user average.
Top 15 Anxiety Medications (Basic Average)
I compiled a separate list of the top anxiolytics with at least 50 reviews – focusing specifically on user average rating (rather than adjusted).
Why? Some medications with fewer reviews may be significantly more effective than adjusted/weighted averages suggest.
- Tramadol: 9.3/10 (107 reviews)
- Valium: 8.7/10 (198 reviews)
- Alprazolam: 8.6/10 (844 reviews) & Xanax5/10 (555 reviews)
- Clonazepam: 8.5/10 (782 reviews)
- Diazepam: 8.4/10 (468 reviews)
- Oxazepam: 8.4/10 (56 reviews)
- Ativan: 8.1/10 (336 reviews)
- Lorazepam: 8/10 (663 reviews)
- Atenolol: 7.9/10 (52 reviews)
- Gabapentin: 7.9/10 (452 reviews)
- Lexapro: 7.5/10 (912 reviews) & Escitalopram: 7.4/10 (1494 reviews)
- Propranolol: 7.4/10 (362 reviews)
- Paxil: 7.2/10 (266 reviews) & Paroxetine: 7.1/10 (369 reviews) & Paxil CR: 8.1/10 (14 reviews)
- Effexor XR: 7/10 (236 reviews) & Venlafaxine: 6.5/10 (408 reviews)
- Lamotrigine: 7/10 (109 reviews)
Others with high ratings fewer reviews (10-50) included: Tranxene: 9.7/10 (15 reviews) & Clorazepate: 9.2/10 (45 reviews); Nefazodone: 9.3/10 (39 reviews); Meprobamate: 8.5/10 (14 reviews); Trifluoperazine: 8.2/10 (10 reviews); Chlordiazepoxide: 7.6/10 (37 reviews); Doxepin: 7/10 (43 reviews).
Limitations with Drugs.com anxiolytic ratings…
There are various limitations associated with using data from Drugs.com for anxiety medication ratings, including:
- Sample sizes: Some medications don’t have many reviews. It’s possible that some medications with few reviews work very well and/or better than those with many reviews – such that the adjusted averages don’t accurately reflect user satisfaction.
- No DB-RCTs: User ratings may be skewed by subjective experiences, the placebo effect, individual physiology, biases related to expectations/prior experiences, etc.
- Confounds: User ratings may conflate efficacy & side effects/adverse events – wherein certain reviewers may give a bad rating based on one side effect (e.g. 1/10 for weight gain) – even if anxiety was reduced OR a good rating (e.g. 10/10 for anxiety reduction) – even though side effects were challenging. Some indivdiuals may be using several medications simultaneously (making it tough to know which is lowering anxiety most).
- Fake reviews: A subset of Drugs.com reviews may be fake – possibly by pharma companies in effort to disort public perception of a medication and increase sales. (If people assume a med is effective – they may be more likely to ask for it from a doctor).
- Polarization: Websites like Drugs.com may attract extreme opinions (e.g. 1/10 “worst drug ever” & 10/10 “best drug ever) – as the extremes might motivate people to review medications more often than average experiences (e.g. 6/10 – worked fairly well).
- Misreporting: A subset of reviews may contain false information (e.g. used Drug X for 10 years instead of 10 months). I’ve even seen some reviews talking about how well a drug worked yet the rating is relaly low (and the opposite: didn’t work at all – 10/10).
Takeaways from user rankings of anxiolytics…
The main takeaway is that medications rated highest by users (adjusted & unadjusted ratings) are not first-line treatments for anxiety disorders.
- Tramadol, an SNRI with mild MOR agonism, remains the highest-ranked medication for anxiety in both adjusted & basic average of user ratings (over 8.5/10) – and may warrant a RCT for anxiety disorders.
- Benzodiazepines seem to provide excellent anxiety relief – such that 7 of the top 10 highest-rated medications are comprised of benzos – with alprazolam, clonazepam, diazepam ranking highest (above 8/10). (Benzos also had significantly more high ratings than lower ratings).
- Gabapentin is highly rated in both adjusted & basic average user ratings – above a 7.5/10 in both – and edges out all antidepressants for anxiety relief. (44% of users gave it a 10/10).
- The best SSRIs/SNRIs for anxiety according to users (adjusted & basic average) are: escitalopram (Lexapro); paroxetine (Paxil); and venlafaxine XR (Effexor XR).
- Propranolol and atenolol are the highest user-rated beta-blockers for managing physical symptoms of anxiety.
- Prochlorperazine is the lowest rated medication for anxiety (79% of users gave it a 1/10). Risperidone, Hydroxyzine, Buspirone, Bupropion – all ranked poorly in adjusted & unadjusted ratings.
- Some of the most polarizing medications (love vs. hate): hydroxyzine (17% 10/10 vs. 27% 1/10); buspirone (21% 10/10 vs. 25% 1/10); venlafaxine (26% 10/10 vs. 22% 1/10); duloxetine (23% 10/10 vs. 23% 1/10).
What about long-term efficacy of anxiolytics (according to user experiences)?
Every single anxiolytic medication that I investigated on Drugs.com (sorting by “Time on Medication”) had a subset of users who were extremely satisfied with its effect even after a long-term (2-years, 5-years, 10-years, 15-years, 20-years).
This included users of benzodiazepines like alprazolam, clonazepam, etc. who use them responsibly at low doses and/or on an as-needed basis (such that tolerance is mitigated or never develops).
The biggest complaints for long-term users were: withdrawal symptoms & discontinuation difficulty; adverse events/side effects; long-term effects; and diminished anxiolytic effect over time (or medication stopped working).
Anxiety medications (mechanisms of action)
There are a variety of mechanisms by which medications effectively treat anxiety – these are the most common:
- Serotonin reuptake inhibition (SSRIs, SNRIs, TCAs)
- GABA modulation (benzodiazepines & barbiturates)
- 5-HT1A receptor agonism (azapirones like buspirone)
- Beta-adrenergic receptor antagonists (propranolol & atenolol)
- Voltage gated ion channel modulation (gabapentinoids & anticonvulsants)
- Histamine receptor antagonists (hydroxyzine & quetiapine)
Other anxiolytic mechanisms…
Below are some additional mechanisms by which certain medications may treat anxiety.
- Alpha receptor agonists (guanfacine & clonidine)
- Monoamine oxidase inhibition (MAOIs)
- Muscarinic acetylcholine receptors (scopolamine & neuroleptics)
- Endocannabinoid modulation (cannabidiol)
- Norepinephrine reuptake inhibition (SNRIs, TCAs, bupropion, atomoxetine)
- Dopamine reuptake inhibition (bupropion, amphetamine, methylphenidate)
- NDMA receptor antagonism (ketamine & memantine)
- Glutamate receptor modulation (mGluR agonists/antagonists)
- Opioidergic system modulation (e.g. MOR agonists, DOR agonists, KOR antagonists)
- Neurosteroid modulation (e.g. allopregnanolone)
- Neuropeptide modulation (oxytocin, substance P, NPY, AVP, CKK, CRF, orexin, etc.)
- Hormonal modulation (e.g. cortisol, testosterone, vasopressin, oxytocin, etc.)
Note: There are probably other mechanisms by which medications treat anxiety – this is not an exhaustive list of mechanisms.
Best anxiolytics according to medical & scientific literature?
I analyzed a variety of medical and scientific sources to determine the best anxiolytics (efficacy & tolerability) as of present.
Drug class ranks: (1) SSRI/SNRI; (2) azapirones, benzos, beta-blockers; (3) TCAs, atypical antidepressants, anticonvulsants, antihistamines, MAOIs; (4) second-gen antipsychotics; (5) cannabinoids.
Meds (adults): (A) escitalopram (Lexapro), sertraline (Zoloft), venlafaxine (Effexor), agomelatine (Valdoxan), duloxetine (Cymbalta), paroxetine (Paxil); (B) benzos, bupropion, pregabalin, hydroxyzine; (C) quetiapine.
Meds (pediatrics): (A) sertraline, fluvoxamine, paroxetine, fluoxetine; (B) guanfacine, atomoxetine, venlafaxine, duloxetine.
StatPearls: Anxiety (R)
Chand & Marwaha (2022) discussed various types of anxiety disorders and medically-appropriate treatment/management strategies.
Authors recommended psychotherapy, pharmacotherapy, or a combination of both – depending on the response of the patient.
- SSRIs: Effective for all anxiety disorders and a first-line treatment.
- SNRIs: Considered as effective as SSRIs and also considered a first-line treatment for GAD.
- Tricyclic antidepressants: Useful in the treatment of anxiety disorders but can cause significant adverse events – so not usually a first-line option.
- Benzodiazepines: Effective for short-term management of anxiety. Ideal for panic attacks or overwhelming episodes of anxiety.
- Buspirone: A mild tranquilizer that is slow-acting and takes ~2 weeks to take effect. Less sedating, non-addictive, and limited withdrawal. Ideal for GAD.
- Beta-blockers: Control the physical symptoms of anxiety like rapid heart rate, trembling voice, sweating, etc. Helpful for phobias like social phobia.
- Cognitive behavioral therapy: Structured, goal-oriented, didactic therapy that focuses on identifying and modifying maladaptive thought patterns and beliefs that trigger anxiety symptoms.
Authors did NOT compare the efficacy OR tolerability of medications – but implied that SSRIs & SNRIs are generally the best first-line pharmacological interventions.
UpToDate: Anxiety Disorders (R)
UpToDate has a series of articles on the treatment of anxiety disorders – but recommendations are contingent upon the specific subtype of anxiety (GAD, SAD, panic disorder, phobias, etc.).
Authors recommend psychotherapy (CBT) and SSRIs as first-line strategies for the management of anxiety disorders – followed by other medications if treatment response is inadequate.
- Psychotherapy (CBT): Recommended as a first-line nonpharmacological intervention for anxiety – the preference(s) of the patient should be considered.
- SSRIs: Recommended as a first-line pharmacological intervention for anxiety. (Citalopram, Escitalopram, Sertraline, Paroxetine, Fluoxetine)
- SNRIs: Recommended as an alternative intervention to SSRIs. (Duloxetine, Venlafaxine extended-release, etc.)
- Buspirone: Sometimes recommended as augmentation option if partial or insufficient response to SSRI/SNRI.
- Gabapentin & Pregabalin: Recommended in some cases, particularly if insufficient response to SSRIs, SNRIs, and buspirone.
- Other antidepressants: Mirtazapine, tricyclic antidepressants (e.g. imipramine), 5-HT1A partial agonists (vilazodone & vortioxetine), MAOIs, etc.
- Antihistamines: Hydroxyzine is sometimes used in persons who haven’t responded to multiple prior medications and augmentation strategies.
- Benzodiazepines: Can be useful in patients without history of substance use disorders for certain types of anxiety for a short-term. (Diazepam & clonazepam preferred due to rapid-onset & long half-life)
- Beta blockers: Can be useful in patients with physical symptoms of anxiety.
- Antipsychotics: Second-generation antipsychotics may exert an anxiolytic effect and can sometimes be useful as an augmentation strategy. (Quetiapine, aripiprazole, etc.)
- Cannabinoids: Preliminary evidence suggests that cannabinoids may help some individuals with anxiety disorders.
2021: Pharmacotherapy for Anxiety Disorders (R)
Melaragno reviewed safety and tolerability of medications used to treat anxiety – and commented on the efficacy of various pharmacological interventions.
- SSRIs & SNRIs: The treatment of choice for the management of generalized anxiety disorder. (Escitalopram, paroxetine, venlafaxine, duloxetine – indications for GAD).
- Buspirone: Approved to treat anxiety disorder and may be useful for those with inadequate response and/or tolerability issues with SSRIs/SNRIs. May be first-line agent for mild-to-moderate GAD for those hesitant to take SSRIs/SNRIs.
- Anticonvulsants: Pregabalin appears effective for the treatment of GAD via alpha-2-delta subunit of voltage gated calcium channels. Gabapentin may have similar efficacy. May be useful for GAD among patients with comorbidities for which gabapentinoids are approved to treat. Others to consider: valproic acid (VPA), levetiracetam, topiramate, tiagabine.
- Benzodiazepines: May benefit patients who fail to respond to multiple SSRIs/SNRIs and/or buspirone. Ideal for short-term/intermittent use among those without history of substance abuse.
- TCAs: Effective for generalized anxiety disorder but should be used with care due to increased risk of adverse events relative to SSRIs/SNRIs. Function similarly via modulation of SERT, NET, and 5-HT receptors. (Imipramine is indicated for the treatment of anxiety – but others may work well too).
- Atypical antidepressants: Bupropion XL appears effective; vortioxetine appears effective; vilazodone appears effective; nefazodone appears effective; trazodone appears effective. Mirtazapine may be useful in some cases as a fifth-line option.
- Antihistamines: Hydroxyzine appears effective for generalized anxiety disorder but causes sedation.
- MAOIs: May be useful in the treatment of panic disorder for some individuals – but higher risk of adverse events compared to conventional treatments.
- Beta blockers: Propranolol & atenolol are the 2 primary agents studied for use in performance-based social anxiety disorder.
- Neuroleptics: Second-generation antipsychotics appear useful – particularly quetiapine. Risperidone, ziprasidone, and aripiprazole may also be effective. Adverse events may be significant – so shouldn’t be used unless other treatments fail.
2020: Comparative Remission Rates & Tolerability of Drugs for GAD (R)
Kong et al. conducted a systematic review and network meta-analysis of DB-RCTs to determine which drugs are most effective & tolerable for the treatment of generalized anxiety disorder.
30 studies were included in the review comprised of 32 DB-RCTs encompassing 13,338 participants with GAD. (28 trials = moderate bias risk; 4 trials = low bias risk).
- Most effective: Agomelatine, Venlafaxine, Escitalopram, Sertraline.
- Best options (efficacy & tolerability): Agomelatine, Sertraline.
Remission rate (rankings)
Authors calculated “SUCRA” (surface under the cumulative ranking curve) and mean ranks for each medication in the treatment of GAD.
- Agomelatine: 89.7 (SUCRA) & 2.1 (mean rank)
- Venlafaxine: 77.2 (SUCRA) & 3.5 (mean rank)
- Escitalopram: 67.1 (SUCRA) & 4.6 (mean rank)
- Sertraline: 64 (SUCRA) & 5.0 (mean rank)
- Quetiapine: 58.6 (SUCRA) & 5.9 (mean rank)
- Duloxetine: 57.6 (SUCRA) & 5.7 (mean rank)
- Paroxetine: 49.2 (SUCRA) & 6.6 (mean rank)
- Pregabalin: 46.3 (SUCRA) & 6.9 (mean rank)
- Lorazepam: 41.2 (SUCRA) & 7.5 (mean rank)
- Vortioxetine: 23.9 (SUCRA) & 9.4 (mean rank)
- Tiagabine: 19 (SUCRA) & 9.9 (mean rank)
- Placebo: 6.2 (SUCRA) & 11.3 (mean rank)
- Sertraline: 88.2 & 2.3
- Vortioxetine: 85.6 & 2.6
- Agomelatine: 82.9 & 2.9
- Placebo: 79.8 & 3.2
- Pregabalin: 57.2 & 5.7
- Escitalopram: 52.3 & 6.2
- Tiagabine: 46 & 6.9
- Duloxetine: 35.2 & 8.1
- Paroxetine: 30.7 & 8.6
- Venlafaxine: 31.6 & 8.6
- Quetiapine: 7.4 & 11.2
- Lorazepam: 3.2 & 11.7
2019: Pharmacological treatments for generalized anxiety disorder (R)
Slee et al. conducted a systematic review & meta-analysis in effort to determine the most effective treatment options for generalized anxiety disorder.
89 RCTs encompassing 25,441 patients were included in the analysis – along with 22 different active drugs or placebo.
Some drugs have significantly more trials and/or participants than others (e.g. 1 trial/31 participants for ocinaplon vs. 17 trials/1862 participants for paroxetine) – so don’t assume efficacy & tolerability order are accurate.
- Highest efficacy: Ocinaplon (7.90); Bupropion (5.30); Quetiapine (3.60); Agomelatine (3.55); Duloxetine (3.13); Mirtazapine (3.12); Hydroxyzine (3.00); Sertraline (2.88).
- Lowest efficacy: Maprotiline (0.38), Imipramine (0.59), Tiagabine (0.77), Vilazodone (1.45), Opipramol (1.92).
- Most tolerable: Agomelatine (0.67), Ocinaplon (0.74), Buspirone (0.76), Pregabalin (0.80) – were notably more acceptable than the placebo. (Bupropion, Escitalopram, Hydroxyzine, Venlafaxine, Sertraline – also similar acceptability to placebo).
- Least tolerable: Citalopram (3.62), Mirtazapine (3.36), Imipramine (2.83), Maprotiline (2.32), Vilazodone (1.59), Quetiapine (1.44), Benzos (1.43), Fluoxetine (1.36).
Limitations of this study include: trials done in different settings; assumption that trials were similar; potential publication bias; open loops in network; not every medication included.
2019: Efficacy & tolerability of pharmacotherapy for pediatric anxiety disorders (R)
Dobson et al. investigated the efficacy and tolerability of pharmacotherapy for pediatric anxiety disorders using network meta-analysis.
22 RCTs (24 treatment arms) encompassing 2,623 patients & 13 medications met inclusion criteria for the analysis.
Medication Classes (Ranked)
SSRIs were the best medication class on composite (efficacy & tolerability).
SNRIs were the second-best medication class on composite (efficacy & tolerability).
A2 agonists were highly effective (based on just 1 trial) but weren’t very tolerable.
Benzodiazepines were extremely tolerable but weren’t very effective.
5-HT1A agonists were the worst class in terms of efficacy and tolerability.
- SSRIs: Efficacy = 88% SUCRA & Tolerability = 69% SUCRA.
- SNRIs: Efficacy = 59% SUCRA & Tolerability = 50% SUCRA.
- TCAs: Efficacy = 48% SUCRA & Tolerability = 38% SUCRA.
- Benzos: Efficacy = 32% SUCRA & Tolerability = 74% SUCRA.
- A2 agonists: Efficacy = 87% SUCRA & Tolerability = 32% SUCRA.
- 5-HT1A agonists: Efficacy = 27% SUCRA & Tolerability = 32% SUCRA.
Specific drugs (Ranked)
I ordered the medications below by efficacy – but listed tolerability as well.
Fluvoxamine exhibited the highest overall efficacy and good tolerability, followed by sertraline and guanfacine – both of which were effective and well-tolerated.
The least effective options were benzodiazepines, buspirone, and clomipramine (TCA) – and the least tolerable options were clonazepam, imipramine, fluoxetine, and buspirone.
- Fluvoxamine: Efficacy (84% SUCRA) & Tolerability (65% SUCRA)
- Sertraline: Efficacy (80% SUCRA) & Tolerability (66% SUCRA)
- Guanfacine: Efficacy (73% SUCRA) & Tolerability (63% SUCRA)
- Paroxetine: Efficacy (63% SUCRA) & Tolerability (69% SUCRA)
- Fluoxetine: Efficacy (66% SUCRA) & Tolerability (30% SUCRA)
- Atomoxetine: Efficacy (64% SUCRA) & Tolerability (56% SUCRA)
- Imipramine: Efficacy (55% SUCRA) & Tolerability (27% SUCRA)
- Venlafaxine: Efficacy (46% SUCRA) & Tolerability (45% SUCRA)
- Duloxetine: Efficacy (41% SUCRA) & Tolerability (49% SUCRA)
- Alprazolam: Efficacy (32% SUCRA) & Tolerability (78% SUCRA)
- Clonazepam: Efficacy (31% SUCRA) & Tolerability (1% SUCRA)
- Buspirone: Efficacy (26% SUCRA) & Tolerability (37% SUCRA)
- Clomipramine: Efficacy (25% SUCRA) & Tolerability (67% SUCRA)
Treatment-emergent suicidality did NOT differ across medication classes. SNRIs were most tolerable & TCAs were least. Sertraline most tolerable for treatment-emergent suicidality & paroxetine least tolerable.
Limitations: Variation in trial design; confounds/comorbidities; treatment-emergent suicidality uncommon (not systematically evaluated in early studies); variability in placebo response & pooling placebo response decreased detection of differences; transitivity; network geometry (2 closed loops & low co-occurrence & homophily); author received financial support from institutions & pharma companies; low number of studies & participants for different medication classes.
2015: Efficacy of treatments for anxiety disorders (R)
Bandelow et al. conducted a meta-analysis in attempt to compare the efficacy of treatments for anxiety disorders (panic disorder, generalized anxiety disorder, social phobia).
Pre-post and treated versus control effect sizes (ES) were calculated for all evaluable randomized controlled trials (RCTs) (N = 234) encompassing 37,333 patients.
- Strengths: Inclusion of a large number of studies
- Limitations: Large effect size heterogeneity; pre-post effect sizes may exaggerate true treatment effect; duration of each intervention; potential publication bias; no unpublished data
Takeaway: The decision on whether to choose psychotherapy vs. medication should be left to the patient – and patients should be informed about the different effect sizes of various treatments & risk/benefit ratios.
Treatment type (Rankings)
Included below are the most effective interventions for anxiety if solely considering treatment type with effect size (pre-post) listed in parentheses next to the intervention.
Understand that some treatment types have bigger effect sizes due to less overall data (e.g. 23 trials for SNRIs vs. 62 trials for SSRIs vs. 15 trials for TCAs vs. 42 trials for benzodiazepines).
For this reason, we shouldn’t assume that an intervention is automatically better than another based solely on effect size (as a low number of trials may be the reason).
- SNRIs (2.25): Venlafaxine & duloxetine.
- SSRIs (2.09): Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline.
- Benzodiazepines (2.15): Alprazolam, bromazepam, clobazam, clonazepam, delorazepam, diazepam, lorazepam.
- CBT + meds (2.12)
- TCAs (1.83): Clomipramine, imipramine, opipramol.
- Psychotherapy (1.30): CBT/exposure, EMDR, IPT, mindfulness, non-face-to-face therapy, psychodynamic therapy, relaxation therapy.
Specific medications (Ranked)
Specific interventions/medications were analyzed in the treatment of anxiety based on pre-post effect sizes (listed in parentheses next to the intervention).
Large effect sizes with just a small number of trials may not be an accurate representation of the medication’s anxiolytic effect (delorazepam has the highest effect but only 1 trial).
- Delorazepam (3.54): 1 trial
- Quetiapine (3.39): 3 trials
- Bromazepam (2.86): 2 trials
- Escitalopram (2.75): 8 trials
- Hydroxyzine (2.56): 4 trials
- Diazepam (2.46): 9 trials
- Lorazepam (2.44): 8 trials
- Paroxetine (2.42): 23 trials
- Venlafaxine (2.32): 20 trials
- Pregabalin (2.30): 8 trials
- Sertraline (2.23): 9 trials
What were the worst anxiety treatments?
Being on a waiting list (50 trials) was the worst intervention for anxiety.
- Waiting list (0.20): 50 trials
- Interpersonal therapy (IPT) (0.78): 4 trials
- Psychological placebo (0.83): 16 trials
- EMDR (1.03): 3 trials
- Citalopram (1.06): 2 trials
- Non-face-to-face therapies (1.11): 33 trials
- Psychodynamic therapy (1.17): 5 trials
- Pill placebo (1.29): 111 trials
- Buspirone (1.35): 7 trials
- Relaxation (1.36): 17 trials
- Moclobemide (1.47): 9 trials
- Fluvoxamine (1.53): 12 trials
2011: Efficacy of drug treatments for GAD (R)
Baldwin et al. conducted a systematic review & meta-analysis comparing the efficacy & tolerability of various drug treatments for generalized anxiety disorder.
A total of 27 RCTs were included in the analysis with sample sizes ranging from 46 to 1,849.
9 drugs were analyzed: duloxetine, escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline, tiagabine, venlafaxine.
- Strengths: Design (robust & transparent); systematic review; published & unpublished studies; standard & prespecified definitions used for response/remission; Bayesian approach; only included DB-RCTs.
- Limitations: All studies sponsored by manufacturers; possible publication bias & study heterogeneity; limited data available for certain treatments; no consideration of covariate effects; comorbidity not examined.
Response: Fluoxetine had the highest probability of being an effective treatment (62.9%). (Ranked: Fluoxetine, venlafaxine, duloxetine, paroxetine, escitalopram, pregabalin, sertraline, lorazepam, tiagabine.)
Remission: Fluoxetine had the highest probability of achieving anxiety remission (60.6%). (Ranked: Fluoxetine, escitalopram, pregabalin, sertraline, lorazepam, tiagabine).
Tolerability: Sertraline had the highest probability of being the most tolerable (49.3%). (Ranked: Sertraline, escitalopram, lorazepam, fluoxetine, venlafaxine, pregabalin, duloxetine, tiagabine, paroxetine).
Strategies for dealing with anxiety disorders…
Anxiety is not the same as an anxiety disorder. Everyone experiences anxiety from time to time – but most people don’t develop a full-blown disorder.
If you have severe anxiety – you’ve probably tried many things and seeking medical care is recommended.
First: Consult medical doctor to rule out preexisting medical conditions that may be causing anxiety. If conditions are found – treat and reassess anxiety level.
1. Environment: Evaluate surroundings. Make an effort to modify your environment in ways that help you manage anxiety. (Natural light, noise reduction, safe neighborhood, greenery, etc.).
2. Social support: Avoid [“toxic”] people who cause you stress and anxiety if possible. Spend time with people who make you feel calm and put you in a good mood if possible.
3. Lifestyle: Physical exercise (cardio & resistance). Nutritious diet. Circadian rhythm optimization (sleep/wake times). Mindfulness. Self-hypnosis. Breathing exercises. Meditation. Work routine. Healthy hobbies.
4. Therapy (CBT): Can effectively treat many anxiety disorders. Type of therapy will depend on the specifics of one’s anxiety. Generally recommended as a nonpharmacological intervention.
5. Supplements: There are a variety of supplements that may help individuals with anxiety, however, the effect will vary depending on the specific user, dosage, and physiological subtype of anxiety.
Talk to a medical doctor and/or pharmacist before using any supplements to ensure that they are safe given your health status, conditions, medications, etc.
Understand that mixing some of these supplements may cause interaction effects – so proceed with caution if using multiple supplements simultaneously.
- Magnesium threonate
- Magnesium glycinate
- Chamomile extract
- Lavender (Silexan)
- Zembrin (herbal SSRI)
- Ashwagandha (calming extract)
- Melatonin (before sleep) (experiment with dosing)
- Glycine (pre-sleep)
- Bacopa (calming extract)
- Kava (infrequent use)
- Selank (synthetic peptide)
- Phenibut (benzo-adjacent)
Note: Supplements listed above contain affiliate links – cost is the same either way. Always appreciated if you buy through my links. (I only link stuff that I’ve used or would use.)
6. Medications: Worth using in severe cases of anxiety. Why? The benefit of anxiety reduction outweighs the risks associated with medications. Severe anxiety can interfere with one’s ability to complete normal tasks & may damage health/shorten lifespan.
- Standard: SSRIs (Specific medication selected based on: age, patient preferences, interaction potential with other meds, health comorbidities, etc.).
- Other options (adjunct & alterantives): SNRIs, buspirone, hydroxyzine, pregabalin, gabapentin, benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam), beta-blockers (propranolol), alpha-2 agonists (clonidine & guanfacine), antipsychotics (quetiapine) – alone or as augmentation options.
- Atypical and/or counterintuitive: Tramadol; Amphetamine; Methylphenidate; Bupropion; Atomoxetine; Modafinil/Armodafinil; Buprenorphine/Naloxone; Naltrexone; Methadone; Caffeine; Minocycline; Memantine. (Could be considered in patients with comorbidities)
Some individuals may want to cycle medications or use “as-needed” (to prevent tolerance) – especially with benzodiazepines.
Using the lowest-necessary dose of medications for anxiety relief is recommended to reduce likelihood of severe side effects/adverse events & withdrawal symptoms.
7. Last resort: Neurostimulation (TMS, Deep Brain Stimulation, Vagus Nerve Stimulation, ECT); Ketamine-infusion; Psilocybin; MDMA-assisted therapy; Heat/Cold Therapy; Sleep Restriction; Psychosurgery; Brain Implant; etc..
Note: Treatment preferences may vary depending on the specific psychiatrist/medical doctor. The above are not formal treatment guidelines.
Have you tried any anxiety medications?
Did the medications help with your anxiety?
Which specific anxiolytics did you use? Which did you find effective or ineffective?
Which anxiolytic worked best for you? (How severe was your anxiety 1-10 & what type? Social vs. generalized vs. PTSD vs. phobia, etc.)
How long did you use the anxiolytic(s)? Did the medication(s) work well the entire time? (Or did they stop working – wherein you had to increase the dose or stop using?)
Did you experience any unwanted adverse reactions or long-term effects?