Selective serotonin reuptake inhibitor in the context of Sertraline

Disorders of diminished motivation (DDM) are a group of disorders involving diminished motivation and associated emotions. Many different terms have been used to refer to diminished motivation. Often however, a spectrum is defined encompassing apathy, abulia, and akinetic mutism, with apathy the least severe and akinetic mutism the most extreme.

DDM can be caused by psychiatric disorders like depression and schizophrenia, brain injuries, strokes, and neurodegenerative diseases. Damage to the anterior cingulate cortex and to the striatum, which includes the nucleus accumbens and caudate nucleus and is part of the mesolimbic dopamine reward pathway, have been especially associated with DDM. Diminished motivation can also be induced by certain drugs, including antidopaminergic agents like antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and cannabis, among others.

Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.

Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal thinking and behavior when taken by children, adolescents, and young adults. Discontinuation syndrome, which resembles recurrent depression in the case of the SSRI class, may occur after stopping the intake of any antidepressant, having effects which may be permanent and irreversible. Tapering off medications gradually is shown to reduce the risk of withdrawal complications.

Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder and seasonal affective disorder and to support smoking cessation. A norepinephrine–dopamine reuptake inhibitor (NDRI), it is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: It does not usually cause sexual dysfunction, it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate-release formulation, carries a higher risk of seizure than many other antidepressants; hence, caution is recommended in patients with a history of seizure disorder. The medication is taken by mouth.

Common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating. Raised blood pressure is notable. Rare but serious side effects include seizures, liver toxicity, psychosis, and risk of overdose. Bupropion use during pregnancy may be associated with increased likelihood of congenital heart defects.

Hallucinogen persisting perception disorder (HPPD) is a non-psychotic disorder in which a person experiences lasting or persistent visual hallucinations or perceptual distortions after using drugs. This includes after psychedelics, dissociatives, entactogens, tetrahydrocannabinol (THC), and SSRIs. Despite being a hallucinogen-specific disorder, the specific contributory role of psychedelic drugs is unknown.

Symptoms may include visual snow, trails and after images (palinopsia), light fractals on flat surfaces, intensified colors, altered motion perception, pareidolia, micropsia, and macropsia. Floaters and visual snow may occur in other conditions.

Monoamine oxidase inhibitors (MAOIs) are a class of drug that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). MAOIs are effective antidepressants due to their specialized function of the inhibition of the enzyme that is responsible for neurotransmitter degradation in the synaptic cleft. This is especially true for treatment-resistant depression, which is a type of depression that is resistant to common treatments of typical depression, such as selective-serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

MAOIs are also utilized to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI or TUI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. Monoamine structures (including neurotransmitters) contain a singular amino group (mono) linked to an aromatic ring by a chain of two carbons. SNDRIs prevent reuptake of these monoamine neurotransmitters through the simultaneous inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively, increasing their extracellular concentrations and, therefore, resulting in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. SNDRIs were developed as potential antidepressants and treatments for other disorders, such as obesity, cocaine addiction, attention-deficit hyperactivity disorder (ADHD), and chronic pain. The increase in neurotransmitters through triple reuptake inhibition (including the addition of dopaminergic action) has the potential to heighten therapeutic effects in comparison to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), reducing symptoms of depression and anxiety in people struggling with mental illness, as well as potentially combating other ailments such as those listed above.

However, increased side effects and abuse potential are concerns when using these agents relative to their SSRI and SNRI counterparts. Additionally, SNDRIs include the naturally occurring drug cocaine, a widely used recreational and often illegal drug for the euphoric effects it produces. Ketamine and phencyclidine are also SNDRIs and are similarly encountered as drugs of abuse. To a lesser extent, MDMA also acts as a SNDRI.

Serotonin syndrome (SS) consists of a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate, usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.

Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. These may include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John's wort, triptans, MDMA, metoclopramide, or cocaine. It occurs in about 15% of SSRI overdoses. It is a predictable consequence of excess serotonin on the central nervous system. Onset of symptoms is typically within a day of the extra serotonin.

The raphe nuclei (Greek: ῥαφή, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the release of serotonin. The anxiolytic drug Buspirone acts as partial agonist against these receptors. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.