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 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736946/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712503/ https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087089/ https://en.wikipedia.org/wiki/Antidepressant https://en.wikipedia.org/wiki/Atypical_antidepressant https://www.sciencedirect.com/topics/neuroscience/antidepressants http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm[Google Scholar] https://www.fda.gov/forconsumers/consumerupdates/ucm095980.htm Show More