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Selective serotonin reuptake inhibitor: Difference between revisions
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==Mechanism of action== | ==Mechanism of action== | ||
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. SSRIs show weak or negligible affinities for the [[noradrenaline]] and [[dopamine|dopamine transporter]]s. | 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 or negligible affinities for the [[noradrenaline]] and [[dopamine|dopamine transporter]]s. | ||
SSRIs also lead to an increased level of cAMP (cyclic adenosine monophosphate), BDNF (brain-derived neurotrophic factor), and several other regulatory neuromodulators. Different SSRIs have different binding profiles, | SSRIs also lead to an increased level of cAMP (cyclic adenosine monophosphate), BDNF (brain-derived neurotrophic factor), and several other regulatory neuromodulators. Different SSRIs have different binding profiles, leading to slightly 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> | ||
==Subjective effects== | ==Subjective effects== | ||
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|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Sedation]]''' ''or'' '''[[Effect::stimulation]]''' - Some SSRIs are sedating (paroxetine and fluvoxamine), whereas some are mildly stimulating (sertraline and fluoxetine). | *'''[[Effect::Sedation]]''' ''or'' '''[[Effect::stimulation]]''' - Some SSRIs are sedating (paroxetine and fluvoxamine), whereas some are mildly stimulating (sertraline and fluoxetine). | ||
*'''[[Effect::Appetite | *'''[[Effect::Physical fatigue]]''' | ||
*'''[[Effect::Decreased libido]]''' - | *'''[[Effect::Appetite enhancement]]''' ''or'' '''[[Effect::appetite suppression]]''' | ||
*'''[[Effect::Orgasm depression]]''' - This effect is dose-dependent and causes delayed orgasm, but in some people, especially older users, | *'''[[Effect::Decreased libido]]''' - Decreased libido and sexual dysfunction are among the most commonly reported side effects of SSRIs. In some cases these effects may persist after use is discontinued, this is known as PSSD.<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 depression]]''' - This effect is dose-dependent and causes delayed orgasm, but in some people, especially older users, SSRIs can make one completely unable to reach orgasm. This is usually treated by either switching to a different antidepressant, or adding an NDRI such as [[bupropion]]. Short-acting SSRIs such as dapoxetine are approved drugs for premature ejaculation. | |||
*'''[[Effect::Pain relief]]''' - Some studies suggest they can be effective as analgesics (painkillers).<ref>https://www.med.unc.edu/ibs/files/2017/10/IBS-and-Antidepressants.pdf</ref> | *'''[[Effect::Pain relief]]''' - Some studies suggest they can be effective as analgesics (painkillers).<ref>https://www.med.unc.edu/ibs/files/2017/10/IBS-and-Antidepressants.pdf</ref> | ||
*'''[[Effect::Nausea]]''' - Nausea is mild and is usually only present upon first introduction and usually subsides after 6-8 weeks. | |||
*'''[[Effect::Headaches]]''' - Headaches are usually only present upon first introduction and usually subside after 6-8 weeks. | |||
*'''[[Effect::Pupil dilation]]''' | *'''[[Effect::Pupil dilation]]''' | ||
*'''[[Effect::Physical fatigue]]''' | *'''[[Effect::Physical fatigue]]''' | ||
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}} | }} | ||
{{effects/visual| | |{{effects/visual| | ||
SSRIs are capable of inconsistently inducing changes in visual perception - often during the beginning of treatment. | SSRIs are capable of inconsistently inducing changes in visual perception - often during the beginning of treatment. | ||
Most effects disappear after a few weeks of treatment but may reappear or become more prominent when combined with [[cannabis]] or [[amphetamines]]. | Most effects often disappear after a few weeks of treatment but may reappear or become more prominent when combined with [[cannabis]] or [[amphetamines]]. | ||
==== | ====Enhancements==== | ||
*'''[[Effect::Visual acuity enhancement]]''' | *'''[[Effect::Visual acuity enhancement]]''' | ||
*'''[[Effect:: | *'''[[Effect::Colour enhancement]]''' - this effect is relatively mild but well pronounced. | ||
====Distortions==== | ====Distortions==== | ||
*'''[[Effect::Tracers]]''' | *'''[[Effect::Tracers]]''' | ||
*'''[[Effect::Visual drifting|Drifting]]''' ''([[Visual drifting#Melting|melting]], [[Visual drifting#Breathing|breathing]], [[Visual drifting#Morphing|morphing]] and [[Visual drifting#Flowing|flowing]])'' - This effect is most similar in presentation to the same effect from [[amphetamines]] but with a cartoony quality most reminiscent of psychedelics such as [[4-HO-MET]] and [[2C-B]] | |||
====Hallucinatory states==== | |||
*'''[[Effect::Peripheral information misinterpretation]]''' - This often manifests itself as seeing minor movement in the corner of one's eye in the absence of any real stimuli. | |||
}} | }} | ||
{{effects/cognitive| | |||
*'''[[Effect:: | *'''[[Effect::Apathy]]'''<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> | ||
*'''[[Effect::Motivation suppression]]''' ''or'' '''[[Effect::Motivation enhancement]]''' - Lack of motivation is anecdotally reported with SSRIs, though on the other hand, suppression of depression or anxiety may enhance motivation. | |||
*'''[[Effect::Anxiety suppression]]''' | *'''[[Effect::Anxiety suppression]]''' | ||
*'''[[Effect::Cognitive fatigue]]''' | *'''[[Effect::Cognitive fatigue]]''' | ||
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*'''[[Effect::Ego inflation]]''' | *'''[[Effect::Ego inflation]]''' | ||
*'''[[Effect::Emotion suppression]]''' - This effect is similar to but less intense compared to the [[emotion suppression]] induced by antipsychotics. | *'''[[Effect::Emotion suppression]]''' - This effect is similar to but less intense compared to the [[emotion suppression]] induced by antipsychotics. | ||
*'''[[Effect::Emotion enhancement]]''' - Upon first introduction, some users can experience amplified emotions. | |||
*'''[[Effect::Mania]]''' | *'''[[Effect::Mania]]''' | ||
*'''[[Effect:: | *'''[[Effect::Derealization]] | ||
}} | }} | ||
{{effects/paradoxical| | {{effects/paradoxical| | ||
These effects are most often experienced upon first introduction and usually subside after | These effects are most often experienced upon first introduction and usually subside after a couple of weeks. | ||
*'''[[Effect::Nausea]]''' | *'''[[Effect::Nausea]]''' | ||
*'''[[Effect::Headache]]''' | *'''[[Effect::Headache]]''' | ||
*'''[[Effect::Depression]]''' | *'''[[Effect::Depression]]''' | ||
*'''[[Effect::Anxiety]]''' | *'''[[Effect::Anxiety]]''' | ||
*'''[[Effect::Emotion | *'''[[Effect::Emotion enhancement]]''' | ||
*'''[[Effect::Thought disorganization]]''' | *'''[[Effect::Thought disorganization]]''' | ||
*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[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> - 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> experience increase in suicidal and self | *'''[[Effect::Motivation suppression]]''' | ||
*'''[[Effect:: | *'''[[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> - 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> experience increase in suicidal and self harming thoughts and behaviors. This effect usually subsides within 6-8 weeks. | ||
*'''[[Effect::Insomnia]]''' | |||
}} | }} | ||
{{Template talk:effects/withdrawal| | {{Template talk:effects/withdrawal| | ||
*'''[[Effect::Brain zaps]]''' | *'''[[Effect::Brain zaps]]''' | ||
*'''[[Effect::Depression]]''' | *'''[[Effect::Depression]]''' | ||
*'''[[Effect::Anxiety]]''' | *'''[[Effect::Anxiety]]''' | ||
*'''[[Effect::Cognitive disconnection]]''' | |||
*'''[[Effect::Focus suppression]]''' | |||
*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[Effect::Motivation suppression]]''' | |||
*'''[[Effect::Headache]]''' | |||
*'''[[Effect::Dream potentiation]]''' | *'''[[Effect::Dream potentiation]]''' | ||
}} | }} | ||
}} | }} | ||
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===Escitalopram=== | ===Escitalopram=== | ||
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> | 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> | ||
===Fluoxetine=== | ===Fluoxetine=== | ||
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===Sertraline=== | ===Sertraline=== | ||
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 | 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 notable 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. | ||
===Other SSRIs=== | ===Other SSRIs=== | ||
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===Dangerous interactions=== | ===Dangerous interactions=== | ||
*'''[[Dextromethorphan]]''' - Dextromethorphan is a | *'''[[Dextromethorphan]]''' - Dextromethorphan is a serotonin releaser as well as an SSRI, therefore has a potential to cause [[serotonin syndrome]], a potentially deadly condition caused by extremely high serotonin levels. Although serotonin syndrome caused by this combination is uncommon, it is strongly advised not to combine them, especially if either is at a high dose. | ||
*'''[[ | *'''[[Empathogens]]''' - Combining SSRIs with serotonergic empathogens such as [[MDMA]], [[mephedrone]], and [[AMT]] can result in [[serotonin syndrome]]. | ||
*'''[[Tramadol]]''' - Combining | *'''[[Tramadol]]''' - Combining SSRIs with tramadol can cause [[seizures]] and [[serotonin syndrome]]. | ||
*'''Other antidepressants''' - Combining SSRIs with other antidepressants such as tricyclic antidepressants and [[ | *'''Other antidepressants''' - Combining SSRIs with other antidepressants such as tricyclic antidepressants and [[MAOIs]] can result in [[serotonin syndrome]]. Non serotonergic antidepressants such as [[bupropion]] are not dangerous to combine with SSRIs. | ||
==See also== | ==See also== | ||
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[[Category:Antidepressant]] | [[Category:Antidepressant]] | ||
[[Category:Pharmacology]] | [[Category:Pharmacology]] | ||
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