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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>https://psychcentral.com/ | 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 are reported to have fewer side effects than older antidepressants like [[MAOI|monoamine oxidase inhibitors]] and [[tricyclic antidepressants]].{{citation needed}} [[MAOI|Monoamine oxidase inhibitors]] also interact with many other medications and foods, leading to a hypertensive crisis that can potentially be fatal. SSRIs can cause sexual dysfunction and compulsive yawning as side effects. Discontinuation of SSRIs can lead to withdrawal symptoms which include flu-like symptoms, as well as [[brain zaps]]. | SSRIs are reported to have fewer side effects than older antidepressants like [[MAOI|monoamine oxidase inhibitors]] and [[tricyclic antidepressants]].{{citation needed}} [[MAOI|Monoamine oxidase inhibitors]] also interact with many other medications and foods, leading to a hypertensive crisis that can potentially be fatal. SSRIs can cause sexual dysfunction and compulsive yawning as side effects. Discontinuation of SSRIs can lead to withdrawal symptoms which include flu-like symptoms, as well as [[brain zaps]]. | ||
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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. Pure SSRIs show only weak 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), 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== | ||
{{effects/base | {{effects/base | ||
|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Sedation]]''' ''or'' '''[[Effect:: | *'''[[Effect::Sedation]]''' ''or'' '''[[Effect::stimulation]]''' - Some SSRIs are sedating (paroxetine and fluvoxamine), whereas some are mildly stimulating (sertraline and fluoxetine). | ||
*'''[[Effect::Physical fatigue]]''' | *'''[[Effect::Physical fatigue]]''' | ||
*'''[[Effect::Appetite enhancement]]''' ''or'' '''[[Effect:: | *'''[[Effect::Appetite enhancement]]''' ''or'' '''[[Effect::appetite suppression]]''' | ||
*'''[[Effect::Decreased libido]]''' | *'''[[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 | *'''[[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::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::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::Increased perspiration]]''' | *'''[[Effect::Increased perspiration]]''' | ||
*'''[[Effect::Dry mouth]]''' | *'''[[Effect::Dry mouth]]''' | ||
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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 often disappear after a few weeks of treatment but may reappear or become more prominent when | Most effects often disappear after a few weeks of treatment but may reappear or become more prominent when combined with [[cannabis]] or [[amphetamines]]. | ||
====Enhancements==== | ====Enhancements==== | ||
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====Distortions==== | ====Distortions==== | ||
*'''[[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]] | *'''[[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==== | ====Hallucinatory states==== | ||
*'''[[Effect::Peripheral information misinterpretation]]''' - This often manifests itself as seeing minor movement in | *'''[[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| | {{effects/cognitive| | ||
*'''[[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::Emotion enhancement]]''' - Upon first introduction, some users can experience amplified emotions. | *'''[[Effect::Emotion enhancement]]''' - Upon first introduction, some users can experience amplified emotions. | ||
*'''[[Effect::Mania]]''' | *'''[[Effect::Mania]]''' | ||
*'''[[Effect::Derealization]] | |||
}} | }} | ||
{{effects/paradoxical| | {{effects/paradoxical| | ||
These effects are most often experienced upon first introduction. | These effects are most often experienced upon first introduction and usually subside after a couple of weeks. | ||
*'''[[Effect::Nausea]]''' | |||
*'''[[Effect::Headache]]''' | |||
*'''[[Effect::Depression]]''' | *'''[[Effect::Depression]]''' | ||
*'''[[Effect::Anxiety]]''' | *'''[[Effect::Anxiety]]''' | ||
*'''[[Effect::Emotion enhancement]]''' | |||
*'''[[Effect::Thought disorganization]]''' | *'''[[Effect::Thought disorganization]]''' | ||
*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[Effect::Motivation suppression]]''' | *'''[[Effect::Motivation suppression]]''' | ||
*'''[[Effect::Suicidal ideation]]''' <ref>Björkenstam, C., Möller, J., | *'''[[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]]''' | *'''[[Effect::Insomnia]]''' | ||
}} | }} | ||
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*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[Effect::Motivation suppression]]''' | *'''[[Effect::Motivation suppression]]''' | ||
*'''[[Effect:: | *'''[[Effect::Headache]]''' | ||
*'''[[Effect::Dream potentiation]]''' | *'''[[Effect::Dream potentiation]]''' | ||
}} | }} | ||
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===Experience reports=== | ===Experience reports=== | ||
Experience reports can be found here: | Experience reports can be found here: | ||
*[https://erowid.org/experiences/subs/exp_SSRIs.shtml Erowid Experience Vaults: SSRIs] | |||
==Examples== | ==Examples== | ||
===Citalopram=== | ===Citalopram=== | ||
Citalopram is an SSRI sold under the brand name '''Celexa''' in the United States. Citalopram is indicated for the treatment of a major depressive disorder. Citalopram was approved in 1998 by the Food and Drug Administration for the treatment of major depressive disorder.<ref> | Citalopram is an SSRI sold under the brand name '''Celexa''' in the United States. Citalopram is indicated for the treatment of a major depressive disorder. Citalopram was approved in 1998 by the Food and Drug Administration for the treatment of major depressive disorder.<ref>{{cite book | vauthors=((PhD, C. B. N. M.)) | date=5 June 2012 | title=Management of Treatment-Resistant Major Psychiatric Disorders | publisher=Oxford University Press | isbn=9780199974146}}</ref> Citalopram is almost exclusively found as the hydrobromide salt, which is the only form approved by the FDA.<ref>Citalopram | https://www.drugs.com/citalopram.html</ref> | ||
===Escitalopram=== | ===Escitalopram=== | ||
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===Fluoxetine=== | ===Fluoxetine=== | ||
Fluoxetine is an SSRI commonly sold under the brand name '''Prozac'''. Fluoxetine is indicated for the treatment of major depressive disorder, bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Fluoxetine is sometimes used in conjunction with olanzapine (an atypical antipsychotic) to treat bipolar I disorder as well as treatment-resistant depression.<ref>Fluoxetine | https://www.drugs.com/fluoxetine.html</ref>A single pill medication called '''Symbyax''' is a combination of olanzapine and fluoxetine.<ref>Symbyax Prescribing Information | http://pi.lilly.com/us/symbyax-pi.pdf</ref>Fluoxetine is on the World Health Organization's list of essential medicines, a list of medicines needed for a basic and effective health system.<ref>WHO List of Essential Medicines | http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf</ref>Fluoxetine was first FDA approved in 1987. | [[Fluoxetine]] is an SSRI commonly sold under the brand name '''Prozac'''. Fluoxetine is indicated for the treatment of major depressive disorder, bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Fluoxetine is sometimes used in conjunction with olanzapine (an atypical antipsychotic) to treat bipolar I disorder as well as treatment-resistant depression.<ref>Fluoxetine | https://www.drugs.com/fluoxetine.html</ref> A single pill medication called '''Symbyax''' is a combination of [[olanzapine]] and fluoxetine.<ref>Symbyax Prescribing Information | http://pi.lilly.com/us/symbyax-pi.pdf</ref> Fluoxetine is on the World Health Organization's list of essential medicines, a list of medicines needed for a basic and effective health system.<ref>WHO List of Essential Medicines | http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf</ref> Fluoxetine was first FDA approved in 1987. | ||
===Fluvoxamine=== | ===Fluvoxamine=== | ||
Fluvoxamine is an SSRI that is used to treat obsessive-compulsive disorder. Fluvoxamine was first approved by the FDA in 1994.<ref>Fluvoxamine | https://www.drugs.com/cdi/fluvoxamine.html</ref>Fluvoxamine has the greatest affinity for the σ1 (sigma-1) receptor, where it acts as an [[agonist]], which may contribute to its biological effects.<ref>Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship | Fluvoxamine is an SSRI that is used to treat obsessive-compulsive disorder. Fluvoxamine was first approved by the FDA in 1994.<ref>Fluvoxamine | https://www.drugs.com/cdi/fluvoxamine.html</ref> Fluvoxamine has the greatest affinity for the σ1 (sigma-1) receptor, where it acts as an [[agonist]], which may contribute to its biological effects.<ref>{{cite journal | vauthors=((Hashimoto, K.)) | journal=Central Nervous System Agents in Medicinal Chemistry | title=Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship | volume=9 | issue=3 | pages=197–204 | date= September 2009 | issn=1875-6166 | doi=10.2174/1871524910909030197}}</ref> | ||
===Paroxetine=== | ===Paroxetine=== | ||
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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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==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 | |||
*'''[[Cannabis]]''' - | *'''[[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. | ||
*'''[[Depressants]]''' - SSRIs increase the effects of CNS [[depressants]] such as [[alcohol]], [[opioids]], and [[benzodiazepines]]. This effect is | *'''[[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 usually not desired as it may intensify [[disinhibition]] and increase the chance of having a blackout. | |||
===Dangerous interactions=== | ===Dangerous interactions=== | ||
*'''[[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. | *'''[[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]]. | *'''[[Empathogens]]''' - Combining SSRIs with serotonergic empathogens such as [[MDMA]], [[mephedrone]], and [[AMT]] can result in [[serotonin syndrome]]. | ||
*'''[[Tramadol]]''' - Combining SSRIs with tramadol can | *'''[[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== | ||
*[[Psychoactive substance]] | *[[Psychoactive substance]] | ||
*[[Antidepressant]] | *[[Antidepressant]] | ||
==External links== | ==External links== | ||
*[https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor SSRI (Wikipedia)] | *[https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor SSRI (Wikipedia)] | ||
*[https://www.erowid.org/chemicals/ssris/ SSRIs (Erowid Vault)] | *[https://www.erowid.org/chemicals/ssris/ SSRIs (Erowid Vault)] | ||
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{{reflist|2}} | {{reflist|2}} | ||
[[Category:Anxiolytics]] | [[Category:Anxiolytics]] | ||
[[Category:Antidepressant]] | [[Category:Antidepressant]] | ||
[[Category: | [[Category:Pharmacology]] | ||
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