Selective serotonin reuptake inhibitor: Difference between revisions

'''Selective serotonin reuptake inhibitors''' (commonly abbreviated as '''SSRIs''') are a class of pharmaceutical [[antidepressant]] medications. They are commonly prescribed for the treatment of major depressive disorders. Other conditions include anxiety disorders, obsessive-compulsive disorder, migraine, attention-deficit hyperactivity disorder (ADHD), addiction/dependence, and sleep disorders. The exact pharmacological mechanism of action SSRIs is unknown.<ref>http://pi.lilly.com/us/prozac.pdf page 20</ref> They are believed to increase the extracellular level of the [[neurotransmitter]] [[serotonin]], eventually leading to improved mood.{{citation needed}}{{clarify}}

SSRIs are believed to increase the extracellular level of the [[neurotransmitter]] [[serotonin]] by [[Reuptake inhibitor|limiting]] its reuptake into the presynaptic cell, increasing the level of [[serotonin]] in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters. Pure SSRIs show only weak affinities for the [[noradrenaline]] and [[dopamine|dopamine transporter]]s.

SSRIs also lead to an increased level of cAMP (cyclic adenosine monophosphate), brain-derived neurotrophic factor, and several other regulatory neuromodulators. Different SSRIs have different binding profiles, which may lead to different effects.<ref>{{cite book | vauthors=((Kolb, B.)), ((Whishaw, I. Q.)) | date= 2005 | title=An introduction to brain and behavior | publisher=Worth Publishers | edition=2nd ed | isbn=9780716711872}}</ref>

*'''[[Effect::Sedation]]''' ''or'' '''[[Effect::stimulation]]''' - Most SSRIs are sedating while others can be mildly stimulating. The sedation produced by SSRIs is usually very mild during the day, but very intense at night. This can make one unable to stay awake at night, however is usually considered a positive effect by most people, as depression often is accompanied by insomnia.

*'''[[Effect::Decreased libido]]''' - Very common. Could persist as PSSD after discontinuation.<ref>{{cite web|author=Pharmacovigilance Risk Assessment Committee (PRAC)|date=11 June 2019|title=New product information wording – Extracts from PRAC recommendations on signals|url=https://www.ema.europa.eu/en/documents/other/new-product-information-wording-extracts-prac-recommendations-signals-adopted-13-16-may-2019-prac_en.pdf#page=2|publisher=European Medicines Agency|id=EMA/PRAC/265221/2019}}</ref> On the other hand, suppression of depression may enhance libido.

*'''[[Effect::Orgasm suppression]]''' - This effect is usually mild and only delays orgasms, however in some people, particularly older users, SSRIs can make one completely unable to reach orgasm. This is usually treated by either switching to a different antidepressant, or adding a DNRI such as [[bupropion]]. Short-acting SSRIs such as dapoxetine are approved drugs for premature ejaculation.

*'''[[Effect::Amotivational syndrome]]'''<ref>{{cite journal |last1=Barnhart |first1=WJ |last2=Makela |first2=EH |last3=Latocha |first3=MJ |title=SSRI-induced apathy syndrome: a clinical review. |journal=Journal of psychiatric practice |date=May 2004 |volume=10 |issue=3 |pages=196-9 |doi=10.1097/00131746-200405000-00010 |pmid=15330228}}</ref>

These effects are most often experienced upon first introduction.

*'''[[Effect::Suicidal ideation]]'''<ref>{{cite journal | vauthors=((Björkenstam, C.)), ((Möller, J.)), ((Ringbäck, G.)), ((Salmi, P.)), ((Hallqvist, J.)), ((Ljung, R.)) | journal=PLoS ONE | title=An Association between Initiation of Selective Serotonin Reuptake Inhibitors and Suicide - A Nationwide Register-Based Case-Crossover Study | volume=8 | issue=9 | pages=e73973 | date=9 September 2013 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767591/ | issn=1932-6203 | doi=10.1371/journal.pone.0073973}}</ref> - Upon first introduction, some users (especially people under the age of 25)<ref>{{Citation | title=What to know about antidepressants for kids and teens | url=https://www.mayoclinic.org/diseases-conditions/teen-depression/in-depth/antidepressants/art-20047502}}</ref> can experience increase suicidal and self harming thoughts and behaviors. This effect usually subsides within 6-8 weeks.

*'''[[Effect::Headaches]]'''

Escitalopram is an SSRI sold under the brand name '''Lexapro''' in the United States. Escitalopram is indicated for the treatment of major depressive disorder and anxiety disorders. It is the s-enantiomer of citalopram, and both have similar efficacy. Escitalopram was FDA approved in 2002.<ref>Escitalopram | https://www.drugs.com/cdi/escitalopram.html</ref> It is a newer SSRI with proved positive effects and less unwanted side effects. Escitalopram in combination with the use of stimulants such as cocaine or amfetamines, increases the risk for heart problems exponentially and thus is highly discouraged.

Sertraline is an SSRI that is sold under the brand name '''Zoloft'''. Sertraline is used to treat major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, anxiety disorders, panic disorder, and premenstrual dysphoric disorder. Sertraline was first FDA approved in 1991.<ref>Sertraline | https://www.drugs.com/sertraline.html</ref>Unlike most SSRIs, sertraline, has somewhat significant activity at the [[dopamine]] transporter protein<ref>{{cite journal | vauthors=((Owens, J. M.)), ((Knight, D. L.)), ((Nemeroff, C. B.)) | journal=L’Encephale | title=[Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] | volume=28 | issue=4 | pages=350–355 | date= August 2002 | issn=0013-7006}}</ref> and could be considered a serotonin-dopamine reuptake inhibitor.

A wide array of substances is contraindicated with SSRIs. Substances that increase extracellular serotonin may increase the risk of [[serotonin syndrome]], particularly substances like [[MDMA]], [[dextromethorphan]], [[tramadol]] and [[pethidine]]. Independent research should be done before taking any substances while on an SSRI to ensure there is no drug interaction. Some dietary supplements such as [[5-HTP]] and St. John's Wort can lead to serotonin syndrome if taken by someone currently medicated with an SSRI.

*'''[[Psychedelics]]''' - Due do the downregulation of 5-HT_2A receptors caused by SSRIs, psychedelics can have a reduced effect. SSRIs can also reduce the chance of having a [[bad trip]] due to its [[Anxiety suppression|anxiolytic]] effects.

*'''[[Cannabis]]''' - While on SSRIs, the [[anxiety]] and [[paranoia]] experienced on cannabis may be less intense, or not experienced at all.

*'''[[Depressants]]''' - SSRIs increase the effects of CNS [[depressants]] such as [[alcohol]], [[opioids]], and [[benzodiazepines]]. This effect is sometimes not desired as it may intensify [[disinhibition]] and increase the chance of having a blackout.

*'''[[Empathogens]]''' - Combining SSRIs with serotonergic empathogens such as [[MDMA]], [[mephedrone]], and AMT can result in [[serotonin syndrome]].

*'''[[Tramadol]]''' - Combining SSRIs with tramadol can result in [[serotonin syndrome]].

*'''Other antidepressants''' - Combining SSRIs with other antidepressants such as tricyclic antidepressants and [[MAOI|MAOIs]] can result in [[serotonin syndrome]]. Non serotonergic antidepressants such as [[bupropion]] are not dangerous to combine with SSRIs.