SSRIs (Selective Serotonin Reuptake Inhibitors)/SNRIs; Types

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder and anxiety disorders. It is an antidepressant that helps to relieve symptoms of depression such as low mood, irritability, feelings of worthlessness, restlessness, anxiety, and difficulty in sleeping. They are one of the most commonly prescribed antidepressants because they are effective at improving mood with fewer or less severe side effects compared.

Types of Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs)

• Citalopram
• Escitalopram
• Paroxetine
• Fluoxetine
• Fluvoxamine
• Sertraline

Indalpine and zimelidine were also formerly used as antidepressants but were withdrawn from the market.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

• Desvenlafaxine
• Duloxetine
• Levomilnacipran
• Milnacipran
• Venlafaxine

Serotonin modulators and stimulators (SMS)

• Vilazodone
• Vortioxetine

Serotonin antagonists and reuptake inhibitors (SARIs)

• Nefazodone – withdrawn/discontinued in most countries
• Trazodone

Etoperidone may also have been formerly used as an antidepressant, but has been discontinued.

Norepinephrine reuptake inhibitors (NRIs)

• Reboxetine
• Teniloxazine – also a 5-HT_2A receptor antagonist
• Viloxazine

Although marketed as an antidepressant, a meta-analysis found that reboxetine was ineffective and potentially harmful. Atomoxetine is also sometimes used as an antidepressant but is not specifically approved for this purpose.

Norepinephrine-dopamine reuptake inhibitors (NDRIs)

• Bupropion – weak NDRI, although its dopaminergic actions are controversial; may act as a norepinephrine-dopamine releasing agent (NDRA) alternatively or additionally; also a non-competitive antagonist of nicotinic acetylcholine receptors

Amineptine and nomifensine were also formerly marketed, but have since been withdrawn due to toxicity. Methylphenidate is also sometimes used as an antidepressant but is not specifically approved for this purpose. Lisdexamfetamine an NDRA was found to be ineffective as an adjunctive antidepressant in phase III clinical trials.

Mechanism of action of Selective serotonin reuptake inhibitors (SSRIs)

In the brain, messages are passed from a nerve cell to another via a chemical synapse, a small gap between the cells. The presynaptic cell that sends the information releases neurotransmitters including serotonin into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient postsynaptic cell, which upon this stimulation, in turn, relays the signal. About 10% of the neurotransmitters are lost in this process; the other 90% are released from the receptors and taken up again by monoamine transporters into the sending presynaptic cell, a process called reuptake.SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and may repeatedly stimulate the receptors of the recipient cell. In the short run, this leads to an increase in signaling across synapses in which serotonin serves as the primary neurotransmitter. On chronic dosing, the increased occupancy of post-synaptic serotonin receptors signals the pre-synaptic neuron to synthesize and release less serotonin. Serotonin levels within the synapse drop, then rise again, ultimately leading to downregulation of post-synaptic serotonin receptors. Other, indirect effects may include increased norepinephrine output, increased neuronal cyclic AMP levels, and increased levels of regulatory factors such as BDNF and CREB. Owing to the lack of a widely accepted comprehensive theory of the biology of mood disorders, there is no widely accepted theory of how these changes lead to the mood-elevating and anti-anxiety effects of SSRIs.

Indications/Uses of Selective serotonin reuptake inhibitors (SSRIs)

SSRIs or SNRIs are used primarily in the clinical treatment of mood disorders such as

• Major depressive disorder  
• Dysthymia, and treatment-resistant variants. They are also used in the treatment of a number of other medical disorders, including
• Anxiety disorders 
• Generalized anxiety disorder 
• Social phobia
• Social anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder 
• Post-traumatic stress disorder 
• Body dysmorphic disorder
• Anorexia nervosa and bulimia nervosa, certain
• Personality disorders such as
• Borderline personality disorder   
• Attention-deficit hyperactivity disorder 
• Parkinson’s disease as well as 
• Chronic pain,
• Neuralgia 
• Neuropathic pain
• Fibromyalgia, 
• A headache, 
• A migraine,
• Smoking cessation, 
• Irritable bowel syndrome 
• Interstitial cystitis 
• Nocturnal enuresis
• Narcolepsy,
• Insomnia, 
• Pathological crying
• Chronic hiccups,
• Schizophrenia.

Contra-Indications

• Syndrome of inappropriate antidiuretic hormone secretion
• Low amount of magnesium in the blood
• Low amount of sodium in the blood
• Low amount of potassium in the blood
• Increased risk of bleeding
• Behaving with excessive cheerfulness and activity
• A mild degree of mania
• Manic-depression
• Having thoughts of suicide
• Neuroleptic malignant syndrome
• Serotonin syndrome – adverse drug interaction
• Closed-angle glaucoma
• Heart attack within the last 30 days
• Very Rapid Heartbeat – Torsades de Pointes
• Prolonged QT interval on EKG
• Heart Disease
• Abnormal EKG with QT changes from Birth
• Liver problems
• Bleeding from Stomach
• Esophagus or Duodenum
• Severe renal impairment
• Seizures
• Risk of angle-closure glaucoma due to narrow-angle of the anterior chamber of the eye

Side Effects of Selective serotonin reuptake inhibitors (SSRIs)

The most common

• Constipation
• Decreased interest in sexual intercourse
• Failure to discharge semen (in men)
• chest pain
• a headache
• joint painPain
• dizziness
• nausea and vomiting
• Severe stomach ache
• epigastric pain,
• diarrhea,
• anorexia,
• flatulence,
• a headache,
• dizziness,
•  fainting, fast or pounding heartbeats.

More common

• Fast or irregular heartbeat
• fever
• Back pain
• dizziness
• a headache
• increased cough
• Acid or sour stomach
• decreased appetite
• Agitation
• chest congestion
• chest pain
• cold sweats
• confusion
• decreased sexual ability or desire
• diarrhea or loose stools
• heartburn
• sleepiness or unusual drowsiness
• stomach or abdominal cramps, gas, or pain
• trouble sleeping

Less common

• Abnormal dreams
• change in sense of taste
• congestion
• discouragement, feeling sad, or empty
• Suicide attempts
• Acting on dangerous impulses
• Aggressive or violent behavior
• Thoughts about suicide or dying
• New or worse depression
• New or worse anxiety or panic attacks
• Agitation, restlessness, anger, or irritability
• Trouble sleeping
• An increase in activity or talking more than normal

Drug Interactions

SSRIs & SNRIs  may interact with the following drugs, supplements & may decrease the efficacy of the drug

• antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine, quetiapine, risperidone)
• barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
• benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• beta-blockers (e.g., carvedilol, metoprolol, propranolol)
• bupropion
• captopril
• carvedilol
• celecoxib
• chloral hydrate
• chloroquine
• cilostazol
• celecoxib
• clopidogrel
• dasatinib
• diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
• domperidone
• glucosamine
• heparin
• herbal products that affect blood clotting (e.g., cat’s claw, chamomile, fenugreek, evening primrose, feverfew, garlic, ginger, ginseng, turmeric)
• ketoconazole
• losartan
• low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• MAO inhibitors (e.g., linezolid, moclobemide, phenelzine, selegiline, tranylcypromine)
• mirabegron
• multivitamins/minerals
• muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine, tizanidine)
• methamphetamine
• metoclopramide
• metoprolol
• narcotic pain relievers (e.g., codeine, fentanyl, methadone, morphine, oxycodone)
• nonsteroidal  anti-inflammatory medications (NSAIDs; diclofenac, ibuprofen, naproxen)
• omega-3 fatty acids
• pentoxifylline
• quinolone antibiotics (e.g., levofloxacin, moxifloxacin)
• seizure medications (e.g., carbamazepine, clobazam,  felbamate, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
• serotonin/norepinephrine reuptake inhibitors (SNRIs e.g., desvenlafaxine, duloxetine, venlafaxine)
• other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, )
• 5-HT3 antagonists (e.g., granisetron, ondansetron)
• tamsulosin
• tapentadol
• thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
• tramadol
• tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine, desipramine)
• tyrosine kinase inhibitor (e.g., imatinib, lapatinib, pazopanib, sunitinib)
• vitamin E
• warfarin

References

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