For the purpose of treating mood disorders, three specific neurotransmitters are targeted, each of which is associated with mood elevation:. It is strongly believed that low levels of these neurotransmitters or the lack of cellular receptors able to receive the messages play a pivotal role in mood disorders.
Moreover, depending on which neurotransmitters or neuroreceptors are low, the type and severity of a mood disorder can differ. Reuptake means reabsorption.
It is a normal mechanism by which the body controls how long a nerve signal lasts. However, if you have significantly low levels of a neurotransmitter, reuptake can be a problem as it restricts the amount of neurotransmitters being actively circulated in the brain. To this end, limiting reuptake increases the extracellular concentrations of these chemicals and, by doing so, increases their ability to exert positive effects on your mood.
Because reuptake inhibitors limit the reabsorption of certain neurotransmitters, these medications are able to increase the availability of these neurotransmitters in the brain. The reuptake inhibitors used to treat mood disorders are classified by the types of neurotransmitter pathway they block.
The drugs are able to do this by binding one or several different proteins, called transporters, which are responsible for carrying the chemical between cells. Some of these reuptake inhibitors are classified as selective because they only bind to certain proteins, while others are nonspecific because they bind to a broad range of proteins.
The choice of reuptake inhibitor depends largely on the condition being treated and the mechanism of action of the drug. SSRIs work by blocking the serotonin transporter in neurons, which results in higher levels and greater activity of the feel-good chemical.
They are typically used to treat major depressive disorder MDD and anxiety disorders. While SSRIs are sometimes used to treat bipolar depression, there is some controversy as to how effective they are given their potential to exacerbate the rapid cycling of moods. SSRI medications approved for use in the U. Symbyax is specially approved for use in treating bipolar depression.
SNRIs block both the serotonin transporter and norepinephrine transporter. However, they are commonly used for short-term therapy, as prolonged use may trigger a manic or hypomanic episode. SNRI medications approved for use in the U. NRIs work by blocking the action of the norepinephrine transporter.
NRI medications approved for use in the U. NDRIs block the action of both the norepinephrine transporter and the dopamine transporter. NDRI medications approved for use in the U. SNDRIs, also known as triple reuptake inhibitors, block the action of the serotonin transporter, norepinephrine transporter, and dopamine transporter. While all these acronyms can be confusing, the good news is that there are many treatment options available for anxiety, depression, and other mood disorders.
Work with your doctor to find a reuptake inhibitor that works best for you. Dealing with racing thoughts? Always feeling tired? These neurotransmitters may contribute to tolerance to opioid therapy and mediate hyperalgesia. Gamma-aminobutyric acid GABA is the major inhibitory neurotransmitter in the brain. It is an amino acid derived from glutamate, which is decarboxylated by glutamate decarboxylase. After interaction with its receptors, GABA is actively pumped back into nerve terminals and metabolized.
Glycine, which resembles GABA in its action, occurs principally in interneurons Renshaw cells of the spinal cord and in circuits that relax antagonist muscles. GABA-A receptors are the site of action for several neuroactive drugs, including benzodiazepines, barbiturates, picrotoxin, and muscimol.
GABA-B receptors are activated by baclofen , used to treat muscle spasms eg, in multiple sclerosis. Serotonin 5-hydroxytryptamine, or 5-HT is generated by the raphe nucleus and midline neurons of the pons and upper brain stem. Tryptophan is hydroxylated by tryptophan hydroxylase to 5-hydroxytryptophan, then decarboxylated to serotonin. Serotonin levels are controlled by the uptake of tryptophan and intraneuronal monoamine oxidase MAO , which breaks down serotonin.
Ultimately, serotonin is excreted in the urine as 5-hydroxyindoacetic acid or 5-HIAA. Selective serotonin receptor agonists eg, sumatriptan can abort migraines.
Acetylcholine is the major neurotransmitter of the bulbospinal motor neurons, autonomic preganglionic fibers, postganglionic cholinergic parasympathetic fibers, and many neurons in the CNS eg, basal ganglia, motor cortex.
It is synthesized from choline and acetyl coenzyme A by choline acetyltransferase, and its action is rapidly terminated via local hydrolysis to choline and acetate by acetylcholinesterase.
Acetylcholine levels are regulated by choline acetyltransferase and by choline uptake. Levels of this neurotransmitter are decreased in patients with Alzheimer disease. Cholinergic receptors are classified as nicotinic N1 in the adrenal medulla and autonomic ganglia or N2 in skeletal muscle or muscarinic M1 through M5 widely distributed in the CNS. M1 occurs in the autonomic nervous system, striatum, cortex, and hippocampus; M2 occurs in the autonomic nervous system, heart, intestinal smooth muscle, hindbrain, and cerebellum.
Dopamine interacts with receptors on some peripheral nerve fibers and many central neurons eg, in the substantia nigra, midbrain, ventral tegmental area, and hypothalamus. The amino acid tyrosine is taken up by dopaminergic neurons and converted by tyrosine hydroxylase to 3,4-dihydroxyphenylalanine dopa , which is decarboxylated by aromatic- l -amino-acid decarboxylase to dopamine. After release and interaction with receptors, dopamine is actively pumped back reuptake into the nerve terminal.
Tyrosine hydroxylase and MAO which breaks down dopamine regulate dopamine levels in nerve terminals. Dopaminergic receptors are classified as D1 through D5. D3 and D4 receptors play a role in thought control limiting the negative symptoms of schizophrenia ; D2 receptor activation controls the extrapyramidal system. However, receptor affinity does not predict functional response intrinsic activity.
For example, ropinirole , which has high affinity for the D3 receptor, has intrinsic activity via activation of D2 receptors. Norepinephrine is the neurotransmitter of most postganglionic sympathetic fibers and many central neurons eg, in the locus caeruleus and hypothalamus.
The precursor tyrosine is converted to dopamine , which is hydroxylated by dopamine beta-hydroxylase to norepinephrine. After release and interaction with receptors, some norepinephrine is degraded by catechol O -methyltransferase COMT , and the remainder is actively taken back into the nerve terminal, where it is degraded by MAO.
Tyrosine hydroxylase, dopamine beta-hydroxylase, and MAO regulate intraneuronal norepinephrine levels. Adrenergic receptors are classified as alpha-1 postsynaptic in the sympathetic system , alpha-2 presynaptic in the sympathetic system and postsynaptic in the brain , beta-1 in the heart , or beta-2 in other sympathetically innervated structures. Endorphins are large polypeptides that activate many central neurons eg, in the hypothalamus, amygdala, thalamus, and locus caeruleus.
The cell body contains a large polypeptide called pro-opiomelanocortin, the precursor of alpha-, beta-, and gamma-endorphins. Pro-opiomelanocortin is transported down the axon and cleaved into fragments; one is beta-endorphin, contained in neurons that project to the periaqueductal gray matter, limbic structures, and major catecholamine-containing neurons in the brain.
After release and interaction with receptors, beta-endorphin is hydrolyzed by peptidases. Enkephalins include met-enkephalin and leu-enkephalin, which are small polypeptides present in many central neurons eg, in the globus pallidus, thalamus, caudate, and central gray matter. Their precursor, proenkephalin, is formed in the cell body, then split by specific peptidases into the active peptides. These substances are also localized in the spinal cord, where they modulate pain signals.
The neurotransmitters of pain signals in the posterior horn of the spinal cord are glutamate and substance P. Enkephalins decrease the amount of neurotransmitter released and hyperpolarize make more negative the postsynaptic membrane, reducing the generation of action potentials and pain perception at the level of the postcentral gyrus. After release and interaction with peptidergic receptors, enkephalins are hydrolyzed into smaller, inactive peptides and amino acids.
Rapid inactivation of exogenous enkephalins prevents these substances from being clinically useful. More stable molecules eg, morphine are used as analgesics instead. Endorphin-enkephalin opioid receptors are classified as mu-1 and mu-2 affecting sensorimotor integration and analgesia , delta-1 and delta-2 affecting motor integration, cognitive function, and analgesia , and kappa-1, kappa-2, and kappa-3 affecting water balance regulation, analgesia, and food intake.
Sigma receptors, currently classified as nonopioid and mostly localized in the hippocampus, bind PCP. New data suggest the presence of many more receptor subtypes, with pharmacologic implications.
Components of the molecular precursor to the receptor protein can be rearranged during receptor synthesis to produce several receptor variants eg, 27 splice variants of the mu opioid receptor.
Also, two receptors can combine dimerize to form a new receptor. Dynorphins are a group of 7 peptides with similar amino acid sequences. They, like enkephalins, are opioids. Substance P, a peptide, occurs in central neurons in the habenula, substantia nigra, basal ganglia, medulla, and hypothalamus and is highly concentrated in the dorsal root ganglia. Its release is triggered by intense afferent painful stimuli. It modulates the neural response to pain and mood; it modulates nausea and vomiting through the activation of NK1A receptors that are localized in the brain stem.
SSRIs block the reabsorption reuptake of serotonin into neurons. This makes more serotonin available to improve transmission of messages between neurons. SSRIs are called selective because they mainly affect serotonin, not other neurotransmitters. SSRIs may also be used to treat conditions other than depression, such as anxiety disorders.
All SSRIs are thought to work in a similar way and generally can cause similar side effects, though some people may not experience any. Many side effects may go away after the first few weeks of treatment, while others may lead you and your doctor to try a different drug. If you can't tolerate one SSRI , you may be able to tolerate a different one, as SSRIs differ in their potencies at blocking serotonin reuptake and in how quickly the body eliminates metabolizes the drug.
Possible side effects of SSRIs may include, among others:. Taking your medication with food may reduce the risk of nausea. Also, as long as your medication doesn't keep you from sleeping, you can reduce the impact of nausea by taking it at bedtime.
Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have. Ask your doctor and pharmacist about the most common possible side effects for your specific SSRI and read the patient medication guide that comes with the prescription. SSRIs are generally safe for most people. However, in some circumstances they can cause problems. For example, high doses of citalopram may cause dangerous abnormal heart rhythms, so doses over 40 milligrams mg a day should be avoided according to the FDA and the manufacturer.
They also recommend a maximum daily dose of 20 mg of citalopram for people over age Issues to discuss with your doctor before you take an SSRI include:. Drug interactions. When taking an antidepressant, tell your doctor about any other prescription or over-the-counter medications, herbs or other supplements you're taking. Some antidepressants can interfere with the effectiveness of other medications, and some can cause dangerous reactions when combined with certain medications or herbal supplements.
For example, SSRIs may increase your risk of bleeding, especially when you're taking other medications that increase the risk of bleeding, such as nonsteroidal anti-inflammatory drugs NSAIDs , aspirin, warfarin Coumadin, Jantoven and other blood thinners. Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to accumulate in your body. Serotonin syndrome most often occurs when two medications that raise the level of serotonin are combined. These include, for example, other antidepressants, certain pain or headache medications, and the herbal supplement St.
John's wort. Signs and symptoms of serotonin syndrome include anxiety, agitation, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure and a rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms. Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.
Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, immediately contact your doctor or get emergency help. Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood. SSRIs aren't addictive.
However, stopping antidepressant treatment abruptly or missing several doses can cause withdrawal-like symptoms. This is sometimes called discontinuation syndrome.
Work with your doctor to gradually and safely decrease your dose. People may react differently to the same antidepressant. For example, a particular drug may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a specific antidepressant than someone else does. Inherited traits play a role in how antidepressants affect you. If you have a close relative who responded to a particular antidepressant, tell your doctor, because this could be a good drug choice to start.
In some cases, results of special blood tests, where available, may offer clues about how your body may respond to a particular antidepressant.
However, other variables can affect your response to medication. When choosing an antidepressant, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past. Typically, it may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend some dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.
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