[NOTE: This article has been posted prior to peer review for use in an active research program. This content will be updated with a peer reviewed version as soon as it is available.]
Depression
The American Psychological Association (APA) recommends psychotherapy or the use of second-generation antidepressants (including SSRIs and SNRIs) as the first line initial treatment for adults with depressive disorders.1 In patients for whom first line treatment options are either unacceptable or ineffective, the APA suggests the following behavioral or supplement-based interventions: exercise, bright light therapy, yoga, or St. John’s Wort monotherapy. They note that there is insufficient evidence to recommend tai chi, acupuncture, omega-3 fatty acids, or S-Adenosyl methionine (commercial names SAMe, SAM-E, or AdoMet).
For adolescents, the APA recommends two specific psychotherapy models (cognitive-behavioral therapy or interpersonal psychotherapy adapted for adolescents) or fluoxetine as the first line treatment.1 There is limited information regarding other medication options for adolescents, although the APA recommends against the use of clomipramine, imipramine, mirtazapine, paroxetine, and venlafaxine. The APA notes that there is insufficient evidence to make a recommendation for the treatment of depression in children.
Medications considered second-generation antidepressants include:1,2
- Selective serotonin reuptake inhibitors (SSRIs) – citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft)
- Serotonin and norepinephrine reuptake inhibitors (SNRIs) – desvenlafaxine (Pristiq, Zhedezla), duloxetine (Cymbalta, Drizalma Sprinkle, Irenka), levomilnacipran (Fetzima), venlafaxine (Effexor)
- Norepinephrine-dopamine reuptake inhibitors (NDRIs) – bupropion (Wellbutrin, Forfivo)
- Serotonin antagonist and reuptake inhibitors (SARIs) – nefazodone (Serzone), trazodone (Desyrel, Oleptro)
- Maprotiline (Ludiomil)
- Mirtazapine (Remeron)
- Vilazodone (Viibryd)
- Vortioxetine (Trintellix, Brintellix)
First-generation antidepressants are generally no longer newly prescribed, although patients who have a history of using these medications may continue taking them.2 Medications considered first-generation antidepressants include:
- Tricyclics (TCAs) – amitriptyline (Elavil), amoxapine (Asedin), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), notriptyline (Pamelor), protriptyline (Vivactil)
- Monoamine oxidase inhibitors (MAOIs) – isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), tranylcypromine (Parnate)
Other treatment options that are Food and Drug Administration (FDA) approved for the treatment of depression but are not recommended treatment options include electroconvulsive therapy, transcranial magnetic stimulation, and vagus nerve stimulation.3
There is also limited emerging literature on the potential efficacy of using psychoactive drugs such as ketamine or psilocybin in combination with psychotherapy to treat depression. These treatments are not FDA approved and in some cases use drugs that are federally illegal in the United States.
Anxiety
American Family Physician key recommendations for practice from 2022 note that the two main categories of treatment for anxiety disorders are pharmacotherapy and psychotherapy, especially cognitive behavioral therapy.4 The treatment of anxiety can be more complicated than depression due to the variety of anxiety disorders. Medications that may be used to treat one anxiety disorder may be contraindicated for others.5,6 Because of this, it is difficult to create a list of medications used for the treatment of all anxiety disorders. For example, below is a table of all of the drug classes and drugs recommended by the 2014 Canadian clinical practice guidelines for the management of anxiety disorders.5
Table 1. Recommended treatments for anxiety disorders according to Canadian clinical practice guidelines.*
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Panic Disorder
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SSRIs – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
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SNRIs – duloxetine, milnacipran, venlafaxine
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TCAs – clomipramine, imipramine
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MAOIs – phenelzine, moclobemide, tranylcypromine
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Other antidepressants – bupropion, mirtazapine, reboxetine
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Benzodiazepines – alprazolam, clonazepam, diazepam, lorazepam
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Atypical antipsychotics – olanzapine, quetiapine, risperidone
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Anticonvulsants – divalproex, levetiracetam
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Social Anxiety Disorder (SAD)
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SSRIs – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
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SNRIs – duloxetine, venlafaxine
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SARIs
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TCAs – clomipramine
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MAOIs – phenelzine
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Other antidepressants – bupropion, mirtazapine
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Benzodiazepines – alprazolam, bromazepam, clonazepam
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Atypical antipsychotics – olanzapine
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Anticonvulsants – divalproex, gabapentin, pregabalin, tiagabine, topiramate
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Other treatments – selegiline
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Generalized Anxiety Disorder (GAD)
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SSRIs – citalopram, escitalopram, fluoxetine, paroxetine, sertraline
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SNRIs – duloxetine, venlafaxine
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SARIs – trazodone
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TCAs – imipramine
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Other antidepressants – agomelatine, bupropion, mirtazapine, vortioxetine
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Benzodiazepines – alprazolam, bromazepam, diazepam, lorazepam
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Atypical antipsychotics – quetiapine
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Anticonvulsants – divalproex, pregabalin
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Other treatments – buspirone, hydroxyzine
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Obsessive-Compulsive Disorder (OCD)
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SSRIs – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
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SNRIs – duloxetine, venlafaxine
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TCAs – clomipramine, desipramine
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MAOIs – phenelzine, tranylcypromine
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Other antidepressants – bupropion, mirtazapine
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Opioids - Tramadol
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Post-Traumatic Stress Disorder (PTSD)
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SSRIs – escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
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SNRIs – duloxetine, venlafaxine
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SARIs – trazodone
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TCAs – amitriptyline, imipramine
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MAOIs – moclobemide, phenelzine
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Other antidepressants – bupropion, mirtazapine, reboxetine, tianeptine
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Atypical antipsychotics – aripiprazole, quetiapine, risperidone
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Anticonvulsants – carbamazepine, lamotrigine, topiramate
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Other treatments – buspirone, memantine
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*Table does not include information on adjunctive or contraindicated treatment options.
When it comes to the treatment of GAD, guidelines agree that the first-line recommended treatment is an SSRI.6-8 Clinical practice guideline also uniformly recommend SNRIs, although some recommend it as a first-line treatment5,8 while others it as second-line.6,7
References
- McQuaid J, Lin E, Barber J, et al. Clinical Practice Guideline for the Treatment of Depression Across Three Age Cohorts. American Psychological Association; 2019.
- Gartlehner G, Gaynes BN, Amick HR, et al. AHRQ Comparative Effectiveness Reviews. Nonpharmacological Versus Pharmacological Treatments for Adult Patients With Major Depressive Disorder. Agency for Healthcare Research and Quality (US); 2015.
- Adult & Adolescent Depression Screening, Diagnosis, and Treatment Guideline. Kaiser Permanente; 2024.
- DeGeorge KC, Grover M, Streeter GS. Generalized Anxiety Disorder and Panic Disorder in Adults. Am Fam Physician. Aug 2022;106(2):157-164.
- Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1(Suppl 1):S1. doi:10.1186/1471-244x-14-s1-s1
- Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. May 2014;28(5):403-39. doi:10.1177/0269881114525674
- National Institute for Health and Care Excellence: Guidelines. Generalised anxiety disorder and panic disorder in adults: management. National Institute for Health and Care Excellence (NICE) Copyright © NICE 2020.; 2019.
- Bandelow B, Allgulander C, Baldwin DS, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part I: Anxiety disorders. World J Biol Psychiatry. Feb 2023;24(2):79-117. doi:10.1080/15622975.2022.2086295
