Antidepressants Drugs; Types, Most Common Feature

Antidepressants Drugs; Types, Most Common Feature

Antidepressants are drugs used for the treatment of major depressive disorder and other conditions, including dysthymia, anxiety disorders, obsessive-compulsive disorder, eating disorders, chronic pain, neuropathic pain and, in some cases, dysmenorrhoea, snoring, migraine, attention-deficit hyperactivity disorder (ADHD), addiction, dependence, and sleep disorders. They may be prescribed alone or in combination with other medications.

Types of Antidepressants Drugs

  • Selective serotonin reuptake inhibitors (SSRIs)-Doctors often start by prescribing an SSRI. These medications generally cause fewer bothersome side effects and are less likely to cause problems at higher therapeutic doses than other types of antidepressants are. SSRIs include fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro).
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs).Examples of SNRI medications include duloxetine (Cymbalta), venlafaxine (Effexor XR), desvenlafaxine (Pristiq, Khedezla) and levomilnacipran (Fetzima).
  • Atypical antidepressants. These medications don’t fit neatly into any of the other antidepressant categories. They include trazodone, mirtazapine (Remeron), vortioxetine (Trintellix), vilazodone (Viibryd) and bupropion (Wellbutrin, Aplenzin, Forfivo XL). Bupropion is one of the few antidepressants not frequently associated with sexual side effects.
  • Tricyclic antidepressants. Tricyclic antidepressants — such as imipramine (Tofranil), nortriptyline (Pamelor), amitriptyline, doxepin and desipramine (Norpramin) — tend to cause more side effects than newer antidepressants. So tricyclic antidepressants generally aren’t prescribed unless you’ve tried other antidepressants first without improvement.
  • Monoamine oxidase inhibitors (MAOIs). MAOIs — such as tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan) — may be prescribed, often when other medications haven’t worked, because they can have serious side effects. Using an MAOI requires a strict diet because of dangerous (or even deadly) interactions with foods — such as certain cheeses, pickles and wines — and some medications, including birth control pills, decongestants and certain herbal supplements. Selegiline (Emsam), an MAOI that you stick on your skin as a patch, may cause fewer side effects than other MAOIs. These medications can’t be combined with SSRIs.
  • Other medications. Your doctor may recommend combining two antidepressants, or other medications may be added to an antidepressant to enhance antidepressant effects.

Review of antidepressants: therapeutic mechanism and side-effects.

Antidepressant class Drug Therapeutic action Unwanted pharmacological action Side effect
Tricyclic antidepressants (TCAs) Clomipramine, imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, protriptyline, maprotiline, amoxapine, doxepine Block reuptake transporters for serotonin and norepinephrine, and to a lesser extent dopamine Muscarinic receptor blockade (anticholinergic) Dry mouth, tachycardia, blurred vision, glaucoma, constipation, urinary retention. Sexual dysfunction, cognitive impairment
α1-Adrenoceptor blockade Drowsiness, postural hypotension, sexual dysfunction
Histamine H1receptor blockade Drowsiness, weight gain
Monoamine oxidase inhibitors (MAOIs) Irreversible: phenelzine, tranylcypromine, isocarboxazid Irreversible and nonselective inhibition of monoamine oxidase (MOA) Irreversible blockade of monoamine oxidase Risk of hypertension from dietary amines – tyramine must be avoided, risk of intracerebral haemorrhage
Reversible: moclobemide Reversible and selective inhibition of MOA
Selective serotonin reuptake inhibitors (SSRIs) Fluoxetine
Selective inhibition of 5HT reuptake transporter Agonist of 5HT2C receptor Gastrointestinal: reduced appetite, nausea, constipation, dry mouth
Central nervous: headache, insomnia, anxiety, fatigue, tremor
Other: delayed orgasm, anorgasmia
Norepinephrine and dopamine reuptake inhibitors (NDRIs) Bupropion Blockade of NE and DA reuptake transporters Increased risk of seizures
Dual serotonin and norepinephrine reuptake inhibitors (SNRIs) Venlafaxine duloxetine Blockade of 5HT and NE reuptake transporters Nausea, dizziness, headache, dry mouth, insomnia, increases in blood pressure
Dual 5HT-2 receptor antagonist/5HT reuptake inhibitors SARIs) Trazodone Powerfully blocks serotonin-2 receptors with less potent inhibition of 5HT reuptake Histamine H1receptor blockade Sedation, cognitive impairment
α1-Adrenoceptor blockade Lowers blood pressure, postural hypotension
Other: priapism (prolonged erections)
Nefazodone Histamine H1receptor blockade Sedating, however less so than Trazodone
Noradrenaline and serotonin specific antidepressant (NASSA) Mianserin mirtazapine 5HT2 antagonism
α1-Adrenoceptor antagonism
Histamine H1receptor blockade Drowsiness, dry mouth, sedation, weight gain
Noradrenergic reuptake inhibitor (NARI) Reboxetine Selective inhibition of NA reuptake Muscarinic receptor blockade Dry mouth, constipation, headaches
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Latest Classification of Antidepressants Drugs

Benzodiazepine hypnotics are used for the short-term treatment of insomnia. Benzodiazepines produce sedative, hypnotic, anxiolytic, and muscle relaxant effects. Benzodiazepines shorten sleep latency and reduce the number of awakenings and the time spent in the stage of wakefulness.

All benzodiazepines are controlled substances in schedule IV.

Generic Brand Name
Brotizolam * Lendormin
Estazolam Prosom
Flurazepam Dalmane
Loprazolam* Dormonoct, Havlane, Sonin, Somnovit
Lormetazepam* Loramet, Noctamid
Nitrazepam* Cerson, Mogadon, Nitrazadon, Radedorm
Quazepam Doral
Temazepam Restoril
Triazolam Halcion
NOT approved in the US
Anxiolytics (not approved as hypnotics)
Alprazolam Xanax
Bromazepam Lexotan
Chlordiazepoxide Librium
Clorazepate dipotassium Tranxene, Gen-Xene
Clonazepam Klonopin
Diazepam Valium
Lorazepam Ativan
Midazolam Versed
Oxazepam Serax

Sedating antidepressants

Sedating antidepressants are widely used for insomnia, but are not officially licensed for this indication. Currently doxepin is the only antidepressant approved by the U.S. FDA for the treatment of insomnia.

Generic Brand Name
Amitriptyline* Elavil, Endep, Vanatrip
Doxepin Silenor, Sinequan, Adapin
Mirtazapine* Remeron
Trazodone* Desyrel, Oleptro, Trittico
NOT FDA approved for insomnia


Currently barbiturates are not recommended for routine use for insomnia due to high incidence of tolerance and dependence.

Generic Brand Name
Amobarbital Amytal Sodium
Butabarbital Butisol
Pentobarbital Nembutal
Secobarbital Seconal Sodium

Other sedative-hypnotic agents

Generic/Class Brand Name
Chloral hydrate
(sedative, hypnotic)
Somnote, Noctec, Aquachloral
Dexmedetomidine Precedex, Dexdor, Dexdomitor
Ethchlorvynol Placidyl

Over-the-counter sleep aids

Most of the over-the-counter sleep aids contain sedating antihistamine (histamine type 1 receptor blocker).

Generic Brand Name
Diphenhydramine Benadryl
Doxylamine Unisom SleepTabs, Good Sense Sleep Aid

Dietary supplements, herbal products

Name Class
Melatonin hormone secreted by the pineal gland, available as dietary supplement
Kava herbal product
Passion flower herbal product
St. John’s wort herbal product
Valerian herbal product

“Off-label” Sleep Aids

Generic Brand Name
Atypical antipsychotics
Olanzapine Zyprexa
Quetiapine Seroquel, Seroquel XR
Gabapentin Neurontin
Tiagabine Gabitril
Chlorpheniramine Antagonate, Chlor-Trimeton, Kloromin, Phenetron, Pyridamal 100, Teldrin
Hydroxyzine and its combinations Vistaril, Atarax
Promethazine Phenergan, Remsed
Trimeprazine Temaril, Vallergan


The two classes of psychostimulants indicated for the treatment of ADHD are methylphenidate and amphetamines. Stimulants function by increasing the amount of dopamine and noradrenaline in the brain and stimulating the central nervous system.

Stimulants are the most potent, and also the most effective class of ADHD medications. Stimulants are considered a first line therapy for controlling ADHD symptoms, unless there are contraindications that preclude their use. Methylphenidate and amphetamines are equally effective, with efficacy rates ranging from 70% to 90%.

Stimulants are available in many different formulations including short-acting, intermediate-acting, and long-acting preparations.

Generic name Brand name
Amphetamine Dyanavel XR, Adzenys XR, Evekeo
Amphetamine/ dextroamphetamine salts Adderall, Adderall XR
Dexmethylphenidate Focalin, Focalin XR, Dexedrine, Dextrostat, ProCentra, Zenzedi
Lisdexamfetamine Vyvanse
Methamphetamine Desoxyn
Methylphenidate Ritalin, Ritalin SR, Ritalin LA, Methylin, Methylin ER, Quillichew ER, Quillivant XR, Aptensio XR, Concerta ER, Metadate CD
Methylphenidate transdermal Daytrana
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Non-stimulant medications approved for the treatment of ADHD have different mode of action compared to psychostimulants and are considered non-addictive with more favorable side effect profiles.On the other hand, non-stimulants are generally less effective than stimulants in the treatment of ADHD. The non-stimulants are usually considered second- and third-line medications.

Atomoxetine is a selective norepinephrine reuptake inhibitor with a unique mechanism of action. Atomoxetine is thought to have minimal abuse potential and significantly less withdrawal symptoms than psychostimulants. The main drawback is that atomoxetine doesn’t directly influence dopamine and it may take several weeks before the drug elicits a therapeutic effect.

Two antihypertensive drugs (alpha-2 noradrenergic agonists) are approved by the FDA to treat ADHD. These drugs reduce activity in the central nervous system but are considered less effective than stimulants. Clonidine and guanfacine are considered relatively safe over the long-term.

Generic name Brand name
Selective Norepinephrine Reuptake Inhibitor
Atomoxetine Strattera
Alpha-2 Noradrenergic Agonists
Clonidine extended-release Kapvay
Guanfacine extended-release Intuniv

“Off-label” Medications

There are several medications used to treat attention-deficit hyperactivity disorder “off-label”. While they are not approved for this disease, these medications can improve productivity, concentration, and overall cognitive function. Additionally, many are used as an augmentation strategy to treat patients that have comorbid depression or other disorders.

Generic name Brand name
Short-acting forms Alpha-2 Noradrenergic Agonists
Clonidine Catapres
Guanfacine Tenex
Aripiprazole Abilify
Olanzapine Zyprexa
Quetiapine Seroque
Risperidone Risperdal
Ziprasidone Geodon
Wakefulness-promoting eugeroic() drugs
Armodafinil Nuvigil
Modafinil Nuvigil
Desipramine Norpramin
Imipramine Tofranil
Bupropion Wellbutrin SR, Wellbutrin XL

ADHD medications under investigation

Generic name, Class Brand name
(serotonin modulator and stimulator)
Brintellix, Trintellix
(serotonin-norepinephrine-dopamine reuptake inhibitor)
(serotonin-norepinephrine-dopamine reuptake inhibitor )


Common features of all antidepressants:

  • 1. All antidepressants work by increasing the levels of neurotransmitters (chemical messengers) in the brain.
  • 2. Antidepressants are NOT controlled substances.
  • 3. Antidepressants improve depressive symptoms at about the same rate.

New Antidepressants

Generic Name Brand Name
Vortioxetine (serotonin modulator and stimulator) Brintellix, approved September 2013
Levomilnacipran (SNRI) Fetzima, approved July 2013
Vilazodone (SSRI) Viibryd, approved January 2011

SSRIs (Selective Serotonin Reuptake Inhibitors)

Generic Brand Name
Citalopram Celexa
Escitalopram Lexapro, Cipralex
Fluoxetine Prozac, Sarafem; Pexeva
Fluvoxamine Luvox
Paroxetine Paxil, Paxil CR
Sertraline Zoloft

Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants. SSRIs selectively inhibit the reuptake of serotonin resulting in increased serotonin concentration in the brain.
Main beneficial features of SSRIs over older antidepressants (MAOIs and TCAs):

  • Low overdose toxicity potential.
  • Low risk of severe systemic adverse effects, especially anticholinergic and cardiovascular side effects.

The major drawbacks of SSRIs:

  • Sexual dysfunction, which is the most common SSRI-induced side effect that leads to drug discontinuation.

Tricyclics (TCA)

Generic Brand Name
Amitriptyline Elavil, Endep, Levate
Amoxapine Asendin
Clomipramine Anafranil
Desipramine Norpramin, Pertofrane
Dosulepin Prothiaden, Thaden
Doxepin Adapin, Sinequan
Imipramine Tofranil
Lofepramine Gamanil, Lomont
Maprotiline Deprilept, Ludiomil, Psymion
Mianserin Bolvidon, Norval, Tolvan
Nortriptyline Pamelor
Protriptyline Vivactil
Trimipramine Surmontil
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Tricyclic antidepressants represent the oldest class of drugs for depression. Currently TCAs are considered second-line antidepressants in cases when SSRIs are ineffective or as adjunct therapy with newer drugs. TCAs act as non-selective inhibitors of the reuptake of serotonin and norepinephrine.

Advantages of TCAs:

  • Proven efficacy.
  • Low cost.

Drawbacks of TCAs:

  • Adverse effects such as orthostatic hypotension, anticholinergic effects, cardiovascular effects (arrhythmias and tachycardia).
  • Overdose toxicity.

SNRIs (Serotonin and Noradrenaline Reuptake Inhibitors)

Generic Brand Name
Desvenlafaxine Pristiq
Duloxetine Cymbalta
Levomilnacipran Fetzima
Milnacipran Savella
Venlafaxine Effexor, Effexor XR

Unlike SSRI antidepressants SNRIs block the reuptake of both serotonin and noradrenaline. Generally, SNRIs have side effect profile as SSRIs, but are more likely to produce anticholinergic side effects.

NaSSA (Noradrenergic and Specific Serotonergic Antidepressant)

Generic Brand Name
Mirtazapine Remeron, Remeron SolTab

Mirtazapine enhances the presynaptic release of serotonin and norepinephrine in the brain. It works via antagonist activity in the presynaptic alpha 2-adrenergic receptors.

NDRIs (Norepinephrine and Dopamine Reuptake Inhibitors)

Generic Brand Name
Bupropion Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban; Aplenzin

Miscellaneous Antidepressants

Generic Brand Name
Atomoxetine (Norepinephrine reuptake Inhibitor) Strattera
Agomelatine (5-HT2C receptor antagonist) Valdoxan
(5HT1A receptor agonist)
(5HT2-receptor antagonist)
Nefadar, Serzone
Tandospirone (azapirone, 5HT1A receptor agonist) Sediel
(Serotonin reuptake enhancer)
(5HT2-receptor antagonist, triazolopyridine-derivative)
Desyrel, Apo-Trazodone, Oleptro
(Norepinephrine Reuptake Inhibitor)
Edronax, Vestra
Viloxazine (Norepinephrine Reuptake Inhibitor) Vivalan
(Selective serotonin reuptake inhibitor, Serotonin 5HT 1A receptor agonist)
Serotonin Modulator and Stimulator
Vortioxetine Brintellix
Etrafon, Triavil

Most commonly prescribed

United States: The most commonly prescribed antidepressants in the US 

Drug name Commercial name Drug class Total prescriptions
Sertraline Zoloft SSRI 33,409,838
Citalopram Celexa SSRI 27,993,635
Fluoxetine Prozac SSRI 24,473,994
Escitalopram Lexapro SSRI 23,000,456
Trazodone Desyrel SARI 18,786,495
Venlafaxine (all formulations) Effexor (IR, ER, XR) SNRI 16,110,606
Bupropion (all formulations) Wellbutrin (IR, ER, SR, XL) NDRI 15,792,653
Duloxetine Cymbalta SNRI 14,591,949
Paroxetine Paxil SSRI 12,979,366
Amitriptyline Elavil TCA 12,611,254
Venlafaxine XR Effexor XR SNRI 7,603,949
Bupropion XL Wellbutrin XL NDRI 7,317,814
Mirtazapine Remeron TeCA 6,308,288
Venlafaxine ER Effexor XR SNRI 5,526,132
Bupropion SR Wellbutrin SR NDRI 4,588,996
Desvenlafaxine Pristiq SNRI 3,412,354
Nortriptyline Sensoval TCA 3,210,476
Bupropion ER Wellbutrin XL NDRI 3,132,327
Venlafaxine Effexor SNRI 2,980,525
Bupropion Wellbutrin IR NDRI 753,516



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