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 classDrugTherapeutic actionUnwanted pharmacological actionSide effect
Tricyclic antidepressants (TCAs)Clomipramine, imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, protriptyline, maprotiline, amoxapine, doxepineBlock reuptake transporters for serotonin and norepinephrine, and to a lesser extent dopamineMuscarinic receptor blockade (anticholinergic)Dry mouth, tachycardia, blurred vision, glaucoma, constipation, urinary retention. Sexual dysfunction, cognitive impairment
α1-Adrenoceptor blockadeDrowsiness, postural hypotension, sexual dysfunction
Histamine H1receptor blockadeDrowsiness, weight gain
Monoamine oxidase inhibitors (MAOIs)Irreversible: phenelzine, tranylcypromine, isocarboxazidIrreversible and nonselective inhibition of monoamine oxidase (MOA)Irreversible blockade of monoamine oxidaseRisk of hypertension from dietary amines – tyramine must be avoided, risk of intracerebral haemorrhage
Reversible: moclobemideReversible and selective inhibition of MOA
Selective serotonin reuptake inhibitors (SSRIs)Fluoxetine
paroxetine
sertraline
fluvoxamine
citalopram
escitalopram
Selective inhibition of 5HT reuptake transporterAgonist of 5HT2C receptorGastrointestinal: reduced appetite, nausea, constipation, dry mouth
Central nervous: headache, insomnia, anxiety, fatigue, tremor
Other: delayed orgasm, anorgasmia
Norepinephrine and dopamine reuptake inhibitors (NDRIs)BupropionBlockade of NE and DA reuptake transportersIncreased risk of seizures
Dual serotonin and norepinephrine reuptake inhibitors (SNRIs)Venlafaxine duloxetineBlockade of 5HT and NE reuptake transportersNausea, dizziness, headache, dry mouth, insomnia, increases in blood pressure
Dual 5HT-2 receptor antagonist/5HT reuptake inhibitors SARIs)TrazodonePowerfully blocks serotonin-2 receptors with less potent inhibition of 5HT reuptakeHistamine H1receptor blockadeSedation, cognitive impairment
α1-Adrenoceptor blockadeLowers blood pressure, postural hypotension
Other: priapism (prolonged erections)
NefazodoneHistamine H1receptor blockadeSedating, however less so than Trazodone
Noradrenaline and serotonin specific antidepressant (NASSA)Mianserin mirtazapine5HT2 antagonism
α1-Adrenoceptor antagonism
Histamine H1receptor blockadeDrowsiness, dry mouth, sedation, weight gain
Noradrenergic reuptake inhibitor (NARI)ReboxetineSelective inhibition of NA reuptakeMuscarinic receptor blockadeDry 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.

GenericBrand Name
Hypnotics
Brotizolam *Lendormin
EstazolamProsom
FlurazepamDalmane
Loprazolam*Dormonoct, Havlane, Sonin, Somnovit
Lormetazepam*Loramet, Noctamid
Nitrazepam*Cerson, Mogadon, Nitrazadon, Radedorm
QuazepamDoral
TemazepamRestoril
TriazolamHalcion
NOT approved in the US
Anxiolytics (not approved as hypnotics)
AlprazolamXanax
BromazepamLexotan
ChlordiazepoxideLibrium
Clorazepate dipotassiumTranxene, Gen-Xene
ClonazepamKlonopin
DiazepamValium
LorazepamAtivan
MidazolamVersed
OxazepamSerax

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.

GenericBrand Name
Amitriptyline*Elavil, Endep, Vanatrip
DoxepinSilenor, 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.

GenericBrand Name
AmobarbitalAmytal Sodium
ButabarbitalButisol
PentobarbitalNembutal
Phenobarbital
SecobarbitalSeconal Sodium

Other sedative-hypnotic agents

Generic/ClassBrand Name
Chloral hydrate
(sedative, hypnotic)
Somnote, Noctec, Aquachloral
DexmedetomidinePrecedex, Dexdor, Dexdomitor
EthchlorvynolPlacidyl

Over-the-counter sleep aids

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

GenericBrand Name
DiphenhydramineBenadryl
DoxylamineUnisom SleepTabs, Good Sense Sleep Aid

Dietary supplements, herbal products

NameClass
Melatoninhormone secreted by the pineal gland, available as dietary supplement
Kavaherbal product
Passion flowerherbal product
St. John’s wortherbal product
Valerianherbal product

“Off-label” Sleep Aids

GenericBrand Name
Atypical antipsychotics
OlanzapineZyprexa
QuetiapineSeroquel, Seroquel XR
Anticonvulants
GabapentinNeurontin
TiagabineGabitril
Antihistamines
ChlorpheniramineAntagonate, Chlor-Trimeton, Kloromin, Phenetron, Pyridamal 100, Teldrin
Hydroxyzine and its combinationsVistaril, Atarax
PromethazinePhenergan, Remsed
TrimeprazineTemaril, 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 nameBrand name
AmphetamineDyanavel XR, Adzenys XR, Evekeo
Amphetamine/ dextroamphetamine saltsAdderall, Adderall XR
DexmethylphenidateFocalin, Focalin XR, Dexedrine, Dextrostat, ProCentra, Zenzedi
LisdexamfetamineVyvanse
MethamphetamineDesoxyn
MethylphenidateRitalin, Ritalin SR, Ritalin LA, Methylin, Methylin ER, Quillichew ER, Quillivant XR, Aptensio XR, Concerta ER, Metadate CD
Methylphenidate transdermalDaytrana

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 nameBrand name
Selective Norepinephrine Reuptake Inhibitor
AtomoxetineStrattera
Alpha-2 Noradrenergic Agonists
Clonidine extended-releaseKapvay
Guanfacine extended-releaseIntuniv

“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 nameBrand name
Short-acting forms Alpha-2 Noradrenergic Agonists
ClonidineCatapres
GuanfacineTenex
Antipsychotics
AripiprazoleAbilify
OlanzapineZyprexa
QuetiapineSeroque
RisperidoneRisperdal
ZiprasidoneGeodon
Wakefulness-promoting eugeroic() drugs
ArmodafinilNuvigil
ModafinilNuvigil
Antidepressants
DesipramineNorpramin
ImipramineTofranil
BupropionWellbutrin SR, Wellbutrin XL

ADHD medications under investigation

Generic name, ClassBrand 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 NameBrand 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)

GenericBrand Name
CitalopramCelexa
EscitalopramLexapro, Cipralex
FluoxetineProzac, Sarafem; Pexeva
FluvoxamineLuvox
ParoxetinePaxil, Paxil CR
SertralineZoloft

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)

GenericBrand Name
AmitriptylineElavil, Endep, Levate
AmoxapineAsendin
ClomipramineAnafranil
DesipramineNorpramin, Pertofrane
DosulepinProthiaden, Thaden
DoxepinAdapin, Sinequan
ImipramineTofranil
LofepramineGamanil, Lomont
MaprotilineDeprilept, Ludiomil, Psymion
MianserinBolvidon, Norval, Tolvan
NortriptylinePamelor
ProtriptylineVivactil
TrimipramineSurmontil

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)

GenericBrand Name
DesvenlafaxinePristiq
DuloxetineCymbalta
LevomilnacipranFetzima
MilnacipranSavella
VenlafaxineEffexor, 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)

GenericBrand Name
MirtazapineRemeron, 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)

GenericBrand Name
BupropionWellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban; Aplenzin

Miscellaneous Antidepressants

GenericBrand 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
VortioxetineBrintellix
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 nameCommercial nameDrug classTotal prescriptions
SertralineZoloftSSRI33,409,838
CitalopramCelexaSSRI27,993,635
FluoxetineProzacSSRI24,473,994
EscitalopramLexaproSSRI23,000,456
TrazodoneDesyrelSARI18,786,495
Venlafaxine (all formulations)Effexor (IR, ER, XR)SNRI16,110,606
Bupropion (all formulations)Wellbutrin (IR, ER, SR, XL)NDRI15,792,653
DuloxetineCymbaltaSNRI14,591,949
ParoxetinePaxilSSRI12,979,366
AmitriptylineElavilTCA12,611,254
Venlafaxine XREffexor XRSNRI7,603,949
Bupropion XLWellbutrin XLNDRI7,317,814
MirtazapineRemeronTeCA6,308,288
Venlafaxine EREffexor XRSNRI5,526,132
Bupropion SRWellbutrin SRNDRI4,588,996
DesvenlafaxinePristiqSNRI3,412,354
NortriptylineSensovalTCA3,210,476
Bupropion ERWellbutrin XLNDRI3,132,327
VenlafaxineEffexorSNRI2,980,525
BupropionWellbutrin IRNDRI753,516

References

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