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 paroxetine sertraline fluvoxamine citalopram escitalopram |
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 |
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 |
|---|---|
| Hypnotics | |
| 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 | |
Barbiturates
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 |
| Phenobarbital | |
| 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 |
| Anticonvulants | |
| Gabapentin | Neurontin |
| Tiagabine | Gabitril |
| Antihistamines | |
| Chlorpheniramine | Antagonate, Chlor-Trimeton, Kloromin, Phenetron, Pyridamal 100, Teldrin |
| Hydroxyzine and its combinations | Vistaril, Atarax |
| Promethazine | Phenergan, Remsed |
| Trimeprazine | Temaril, Vallergan |
Psychostimulants
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 |
Non-Stimulants
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 |
| Antipsychotics | |
| Aripiprazole | Abilify |
| Olanzapine | Zyprexa |
| Quetiapine | Seroque |
| Risperidone | Risperdal |
| Ziprasidone | Geodon |
| Wakefulness-promoting eugeroic() drugs | |
| Armodafinil | Nuvigil |
| Modafinil | Nuvigil |
| Antidepressants | |
| Desipramine | Norpramin |
| Imipramine | Tofranil |
| Bupropion | Wellbutrin SR, Wellbutrin XL |
ADHD medications under investigation
| Generic name, Class | Brand name |
|---|---|
| Vortioxetine (serotonin modulator and stimulator) |
Brintellix, Trintellix |
| Centanafadine (serotonin-norepinephrine-dopamine reuptake inhibitor) |
|
| Dasotraline (serotonin-norepinephrine-dopamine reuptake inhibitor ) |
|
| Metadoxine |
Antidepressants
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 |
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 |
| Buspirone (5HT1A receptor agonist) |
Buspar |
| Nefazodone (5HT2-receptor antagonist) |
Nefadar, Serzone |
| Tandospirone (azapirone, 5HT1A receptor agonist) | Sediel |
| Tianeptine (Serotonin reuptake enhancer) |
Stablon |
| Trazodone (5HT2-receptor antagonist, triazolopyridine-derivative) |
Desyrel, Apo-Trazodone, Oleptro |
| Reboxetine (Norepinephrine Reuptake Inhibitor) |
Edronax, Vestra |
| Viloxazine (Norepinephrine Reuptake Inhibitor) | Vivalan |
| Vilazodone (Selective serotonin reuptake inhibitor, Serotonin 5HT 1A receptor agonist) |
Viibryd |
| Serotonin Modulator and Stimulator | |
| Vortioxetine | Brintellix |
| Combinations | |
| Fluoxetine/Olanzapine (SSRI/antipsychotic) |
Symbyax |
| Amitriptyline/Perphenazine (TCA/antipsychotic) |
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 |
References
