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Selective serotonin reuptake inhibitor: Difference between revisions
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'''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}} | '''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 of 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 can be dangerous when used in combination with other substances that increase or modulate serotonin such as [[MDMA]] and [[MAOI|Monoamine Oxidase Inhibitors]] (MAOIs). A combination with these substances can lead to [[serotonin syndrome]] and potentially be fatal. SSRIs do not work for everyone and take 3-6 weeks to start having noticeable effects.<ref>{{Citation | year=2021 | title=Do Antidepressants Work Right Away? | url=https://psychcentral.com/depression/how-long-do-antidepressants-take-to-work}}</ref> | SSRIs can be dangerous when used in combination with other substances that increase or modulate serotonin such as [[MDMA]] and [[MAOI|Monoamine Oxidase Inhibitors]] (MAOIs). A combination with these substances can lead to [[serotonin syndrome]] and potentially be fatal. SSRIs do not work for everyone and take 3-6 weeks to start having noticeable effects.<ref>{{Citation | year=2021 | title=Do Antidepressants Work Right Away? | url=https://psychcentral.com/depression/how-long-do-antidepressants-take-to-work}}</ref> | ||
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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 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 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 | 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, which lead 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 intensification]]''' ''or'' '''[[Effect::appetite suppression]]''' | |||
*'''[[Effect::Appetite | |||
*'''[[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> | *'''[[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> | ||
*'''[[Effect::Orgasm | *'''[[Effect::Orgasm depression]]''' - This effect is dose-dependent and causes delayed orgasm, but in some people, especially older users, an SSRI 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::Pupil dilation]]''' | *'''[[Effect::Pupil dilation]]''' | ||
*'''[[Effect::Physical fatigue]]''' | |||
*'''[[Effect::Increased perspiration]]''' | *'''[[Effect::Increased perspiration]]''' | ||
*'''[[Effect::Dry mouth]]''' | *'''[[Effect::Dry mouth]]''' | ||
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}} | }} | ||
{{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 disappear after a few weeks of treatment but may reappear or become more prominent when combined with [[cannabis]] or [[amphetamines]]. | ||
==== | ====Amplifications==== | ||
*'''[[Effect::Visual acuity enhancement]]''' | *'''[[Effect::Visual acuity enhancement]]''' | ||
*'''[[Effect:: | *'''[[Effect::Color enhancement]]''' - This effect is relatively mild but well pronounced. | ||
====Suppressions==== | |||
*'''[[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. | |||
====Distortions==== | ====Distortions==== | ||
*'''[[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]]. | |||
*'''[[Effect::Tracers]]''' | *'''[[Effect::Tracers]]''' | ||
}} | }} | ||
{{effects/cognitive| | |{{effects/cognitive| | ||
*'''[[Effect:: | *'''[[Effect::Depression reduction]]''' | ||
*'''[[Effect::Anxiety suppression]]''' | *'''[[Effect::Anxiety suppression]]''' | ||
*'''[[Effect::Cognitive fatigue]]''' | *'''[[Effect::Cognitive fatigue]]''' | ||
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*'''[[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::Mania]]''' | *'''[[Effect::Mania]]''' | ||
*'''[[Effect::Motivation depression]]'''<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> | |||
}} | }} | ||
{{effects/paradoxical| | {{effects/paradoxical| | ||
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*'''[[Effect::Depression]]''' | *'''[[Effect::Depression]]''' | ||
*'''[[Effect::Anxiety]]''' | *'''[[Effect::Anxiety]]''' | ||
*'''[[Effect::Emotion | *'''[[Effect::Emotion intensification]]''' | ||
*'''[[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> - | *'''[[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. | ||
*'''[[Effect:: | *'''[[Effect::Wakefulness]]''' | ||
}} | }} | ||
{{Template talk:effects/withdrawal| | {{Template talk:effects/withdrawal| | ||
*'''[[Effect::Brain zaps]]''' | *'''[[Effect::Brain zaps]]''' | ||
*'''[[Effect::Headache]]''' | |||
*'''[[Effect::Depression]]''' | *'''[[Effect::Depression]]''' | ||
*'''[[Effect::Anxiety]]''' | *'''[[Effect::Anxiety]]''' | ||
*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[Effect::Dream potentiation]]''' | *'''[[Effect::Dream potentiation]]''' | ||
*'''[[Effect::Cognitive disconnection]]''' | |||
}} | }} | ||
}} | }} | ||
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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 | 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 noticeable 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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==Drug interactions== | ==Drug interactions== | ||
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 | 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 in combination with an SSRI. | ||
Some NSAID [[pain relief|analgesics]] may increase the risk of excess bleeding in those who take SSRIs. NSAIDs include ibuprofen, aspirin (acetylsalicylic acid), and naproxen. | Some NSAID [[pain relief|analgesics]] may increase the risk of excess bleeding in those who take SSRIs. NSAIDs include ibuprofen, aspirin (acetylsalicylic acid), and naproxen. | ||
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===Combinations=== | ===Combinations=== | ||
*'''[[Psychedelics]]''' - Due do the downregulation of 5-HT<sub>2A</sub> receptors caused by SSRIs, psychedelics can have a reduced effect. SSRIs | *'''[[Psychedelics]]''' - Due do the downregulation of 5-HT<sub>2A</sub> receptors caused by SSRIs, psychedelics can have a reduced effect. SSRIs also reduce the chance of having a [[bad trip]] due to its [[Anxiety suppression|anxiolytic]] effects. | ||
*'''[[Cannabis]]''' - | *'''[[Cannabis]]''' - 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 | *'''[[Depressants]]''' - SSRIs increase the effects of CNS [[depressants]] such as [[alcohol]], [[opioids]], and [[benzodiazepines]]. This effect is usually not desired as it may intensify [[disinhibition]] and increase the chance of having a blackout. | ||
===Dangerous interactions=== | ===Dangerous interactions=== | ||
*'''[[Dextromethorphan]]''' - Dextromethorphan is a | *'''[[Dextromethorphan]]''' - Dextromethorphan is a cough medicine which has a potential to cause [[serotonin syndrome]] in recreational doses. Combination with an SSRI is strongly discouraged. | ||
*'''[[ | *'''[[Entactogen|Entactogens]]''' - Combining SSRIs with serotonin releasers such as [[MDMA]], [[mephedrone]], and [[AMT]] can result in [[serotonin syndrome]]. | ||
*'''[[Tramadol]]''' - Combining | *'''[[Tramadol]]''' - Combining an SSRI with tramadol can cause [[seizure|seizures]] and [[serotonin syndrome]]. | ||
*'''Other antidepressants''' - Combining SSRIs with other antidepressants such as tricyclic antidepressants and [[MAOI|MAOIs]] can result in [[serotonin syndrome]] | *'''Other antidepressants''' - Combining SSRIs with other antidepressants such as tricyclic antidepressants and [[MAOI|MAOIs]] can result in [[serotonin syndrome]] and death. | ||
==See also== | ==See also== | ||