Selective serotonin reuptake inhibitor

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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. They are believed to increase the extracellular level of the neurotransmitter serotonin, eventually leading to improved mood.^{[clarification needed]}

SSRIs can be dangerous when used in combination with other substances that increase or modulate serotonin such as MDMA and 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.

SSRIs are reported to have fewer side effects than older antidepressants like monoamine oxidase inhibitors and tricyclic antidepressants. 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.

A comparison of the structure of commonly prescribed SSRIs.

Mechanism of action

SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by 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 transporters.

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.

Subjective effects

Physical effects

• • Sedation or 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.
  • Physical fatigue
  • Appetite enhancement or appetite suppression
  • Decreased libido - Very common. Could persist as PSSD after discontinuation. On the other hand, suppression of depression may enhance libido.
  • 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.
  • Pain relief - Some studies suggest they can be effective as analgesics (painkillers).
  • Nausea - Nausea is mild and is usually only present upon first introduction and usually subsides after 6-8 weeks.
  • Headaches - Headaches are usually only present upon first introduction and usually subside after 6-8 weeks.
  • Pupil dilation
  • Increased perspiration
  • Dry mouth
  • Vasoconstriction

Visual effects

• 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 combined with cannabis or amphetamines.

  Enhancements

  • Visual acuity enhancement
  • Colour enhancement - this effect is relatively mild but well pronounced.

  Distortions

  • Drifting (melting, breathing, morphing and 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

  • 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.

Cognitive effects

• • Amotivational syndrome
  • Anxiety suppression
  • Cognitive fatigue
  • Focus suppression
  • Dream suppression
  • Ego inflation
  • Emotion suppression - This effect is similar to but less intense compared to the emotion suppression induced by antipsychotics.
  • Emotion enhancement - Upon first introduction, some users can experience amplified emotions.
  • Mania

Paradoxical effects

• These effects are most often experienced upon first introduction.
  • Depression
  • Anxiety
  • Thought disorganization
  • Irritability
  • Motivation suppression
  • Suicidal ideation - Upon first introduction, some users (especially people under the age of 25) can experience increase suicidal and self harming thoughts and behaviors. This effect usually subsides within 6-8 weeks.
  • Insomnia

Withdrawal effects

• • Brain zaps
  • Depression
  • Anxiety
  • Cognitive disconnection
  • Focus suppression
  • Irritability
  • Motivation suppression
  • Headaches
  • Dream potentiation

Experience reports

Experience reports can be found here:

• Erowid Experience Vaults: SSRIs

Examples

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. Citalopram is almost exclusively found as the hydrobromide salt, which is the only form approved by the FDA.

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.

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. A single pill medication called Symbyax is a combination of olanzapine and fluoxetine. Fluoxetine is on the World Health Organization's list of essential medicines, a list of medicines needed for a basic and effective health system. Fluoxetine was first FDA approved in 1987.

Fluvoxamine

Fluvoxamine is an SSRI that is used to treat obsessive-compulsive disorder. Fluvoxamine was first approved by the FDA in 1994. Fluvoxamine has the greatest affinity for the σ1 (sigma-1) receptor, where it acts as an agonist, which may contribute to its biological effects.

Paroxetine

Paroxetine is an SSRI that is sold under the brand name Paxil. Paroxetine is used to treat major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, anxiety disorders, premenstrual dysphoric disorder, and under the brand name Brisdelle, it is used to treat hot flashes related to menopause. Paroxetine was first approved by the FDA in 1992.

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.Unlike most SSRIs, sertraline, has somewhat significant activity at the dopamine transporter protein and could be considered a serotonin-dopamine reuptake inhibitor.

Other SSRIs

Several other SSRIs have been developed and marketed. Dapoxetine is used in some countries to treat premature ejaculation. Indalpine and zimelidine were originally marketed but later withdrawn due to the emergence of Guillain–Barré syndrome, a serious neurological disease. Cericlamine and panuramine were developed but never marketed.

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 by someone currently medicated with an SSRI.

Some NSAID analgesics may increase the risk of excess bleeding in those who take SSRIs. NSAIDs include ibuprofen, aspirin (acetylsalicylic acid), and naproxen.

Most SSRIs inhibit the function of certain cytochrome P450 enzymes that metabolize other substances so that SSRIs may lead to an increased or decreased serum level of certain medications.

Combinations

• 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 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.

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.
• 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 MAOIs can result in serotonin syndrome. Non serotonergic antidepressants such as bupropion are not dangerous to combine with SSRIs.

See also

• Psychoactive substance
• Antidepressant

External links

• SSRI (Wikipedia)
• SSRIs (Erowid Vault)