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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/15 15:55:49」(JST)
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| 「SNRI」はこの項目へ転送されています。ガンダムシリーズの架空の組織については「サナリィ」をご覧ください。 |
セロトニン
ノルアドレナリン
セロトニン・ノルアドレナリン再取り込み阻害薬（セロトニン・ノルアドレナリンさいとりこみそがいやく、SNRI：Serotonin & Norepinephrine Reuptake Inhibitors[1]）は、抗うつ薬の一種。主に大うつ病や気分障害の治療に処方される。不安障害、強迫性障害、ADHDなどでも処方されることがある。
選択的セロトニン再取り込み阻害薬（SSRI）の次の世代の抗うつ薬と言われている。シナプスにおけるセロトニンとノルアドレナリンの再吸収を阻害することで、これらの神経伝達物質の濃度を増加させることによりうつ症状を改善する。SSRIがシナプスで放出されたセロトニンのみの再吸収を阻害し、このセロトニンの濃度を高める事によってうつ状態を改善させるのに加え、SNRIでは更にノルアドレナリンの再吸収を阻害することによって、興奮神経を刺激し、やる気や気分を向上させる効果も発揮する。
従来の三環系抗うつ薬・四環系抗うつ薬より副作用は少ないと言われている。
目次
- 1 薬剤名
- 1.1 日本国内で承認済のもの
- 1.2 日本国内で未承認のもの
- 2 問題点
- 3 脚注
- 4 関連項目
薬剤名
ノルアドレナリン神経におけるSNRIの作用機序。
「一般名（商品名）」という形式で、具体的薬剤を列挙する。
日本国内で承認済のもの
- ミルナシプラン（トレドミン）
- デュロキセチン（サインバルタ[2]）（日本国外では「シンバルタ」としても発売されている。）
日本国内で未承認のもの
- ヴェンラファキシン（エフェクサー）（日本では開発中止）
- ネファゾドン（サーゾーン）
問題点
2013年、日本の厚生労働省は、大うつ病性障害に対し、18歳未満に投与しても効果を確認できなかったとして、添付文書を改訂し医師に慎重な投与を求めるよう日本製薬団体連合会に要請した。対象は「トレドミン」「サインバルタ」、他はSSRIが4製品、NaSSAが2製品の計8製品である[3][4]。
「抗うつ薬#議論」も参照
脚注
- ^ 日本語における「ノルアドレナリン」（またはドイツ語の"Noradrenalin"）と英語における"norepinephrine"（ノルエピネフリン）の名称の相違については、アドレナリン#エピネフリンという名称を参照のこと。
- ^ 抗うつ薬「サインバルタカプセル20mg、30mg」の製造販売承認取得について (PDF) - 塩野義製薬報道者向け資料（2010年1月20日付）
- ^ 「１８歳未満「効果確認できず」＝抗うつ剤の注意改訂要請—厚労省」The Wall Street Journal 日本語版（時事通信社配信）2013年3月29日。
- ^ 「ＳＳＲＩなど抗うつ薬６種類の「使用上の注意」改訂を要請」厚生労働省2013年3月29日。
関連項目
- 抗うつ薬
- 選択的セロトニン再取り込み阻害薬 (SSRI)
- うつ病
- SSRI離脱症候群
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wiki en
Serotonin
Norepinephrine
Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs used in the treatment of major depression and other mood disorders. They are sometimes also used to treat anxiety disorders, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), chronic neuropathic pain, and fibromyalgia syndrome (FMS), and for the relief of menopausal symptoms.
SNRIs are potent inhibitors of serotonin (5-Hydroxytryptamine, 5-HT) and norepinephrine (NE, noradrenalin) reuptake. These neurotransmitters are known to play an important role in mood. These can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act upon serotonin alone.
The human serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of monoamine reuptake can possibly offer advantages over other antidepressants drugs by treating a wider range of symptoms.[1] SNRIs are second-generation agents, such as selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs). Over the past two decades, second-generation agents have gradually replaced first-generation agents, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) as the drugs of choice for the treatment of MDD. This is mainly because of their improved tolerability and safety profile.[2]
Contents
- 1 Overview of SNRIs
- 2 History
- 3 Mechanism of action
- 3.1 Tricyclic antidepressants
- 3.2 Selective serotonin reuptake inhibitors
- 3.3 Selective norepinephrine reuptake inhibitors
- 3.4 Dual serotonin and norepinephrine reuptake inhibitors
- 4 Structure activity relationship (SAR)
- 4.1 Aryloxypropanamine scaffold
- 4.2 Cycloalkanol ethylamine scaffold
- 4.3 Milnacipran
- 4.4 Future development of SAR
- 5 Clinical trials
- 6 Current status
- 7 Products of SNRIs
- 8 Indications
- 9 Pharmacology
- 9.1 Route of Administration
- 9.2 Dosage
- 9.3 Mode of Action
- 9.4 Pharmacodynamics
- 9.5 Pharmacokinetics
- 10 Contraindications
- 11 Side-effects
- 12 Precautions
- 12.1 Starting an SNRI regimen
- 12.2 Discontinuation syndrome
- 13 Overdose
- 13.1 Causes
- 13.2 Symptoms
- 13.3 Management
- 14 Comparison to SSRIs
- 15 See also
- 16 References
Overview of SNRIs
- Venlafaxine (Effexor) – The first and most commonly used SNRI. It was introduced by Wyeth in 1994. The reuptake effects of venlafaxine are dose-dependent. At low doses (<150 mg/day), it acts only on serotonergic transmission. At moderate doses (>150 mg/day), it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day), it also affects dopaminergic neurotransmission.[3]
- Desvenlafaxine (Pristiq)[4] – The active metabolite of venlafaxine. It is believed to work in a similar manner, though some evidence suggests lower response rates compared to venlafaxine and duloxetine. It was introduced by Wyeth in May 2008 and was then the third approved SNRI.[5]
- Duloxetine (Cymbalta, Yentreve)[6] – By Eli Lilly and Company, has been approved for the treatment of depression and neuropathic pain in August 2004. Duloxetine is contraindicated in patients with heavy alcohol use or chronic liver disease, as duloxetine can increase the levels of certain liver enzymes that can lead to acute hepatitis or other diseases in certain at risk patients. Currently, the risk of liver damage appears to be only for patients already at risk, unlike the antidepressant nefazodone, which, though rare, can spontaneously cause liver failure in healthy patients.[7] Duloxetine is also approved for major depressive disorder (MDD), generalized anxiety disorder (GAD), chronic musculoskeletal pain, including chronic osteoarthritis pain and chronic low back pain (as of October, 2010), and is one of the only three medicines approved by the FDA for fibromyalgia [1].
- Milnacipran (Dalcipran, Ixel, Savella)[8] – Shown to be significantly effective in the treatment of depression and fibromyalgia.[9] The Food and Drug Administration (FDA) approved milnacipran for treatment of fibromyalgia in the United States of America in January 2009, however it is currently not approved for depression in that country. Milnacipran has been commercially available in Europe and Asia for several years.
- Levomilnacipran (Fetzima, F2695) – The levo- isomer of milnacipran. Under development for the treatment of depression in the United States and Canada, it was approved by the FDA for treatment of MDD in July 2013.
- Sibutramine (Meridia, Reductil) – An SNRI, which, instead of being developed for the treatment of depression, was widely marketed as an appetite suppressant for weight loss purposes. Sibutramine was the first drug for the treatment of obesity to be approved in 30 years.[10]
- Bicifadine (DOV-220,075) – By DOV Pharmaceutical, potently inhibits the reuptake of serotonin and norepinephrine (and dopamine to a lesser extent), but rather than being developed for the already-crowded antidepressant market, it is being researched as a non-opioid, non-NSAID analgesic.
- SEP-227162 – An SNRI under development by Sepracor for the treatment of depression.
Timeline of approved SNRIs.
History
In 1952 iproniazid, an antimycobacterial agent, was discovered to have psychoactive properties while researched as a possible treatment for tuberculosis. Researchers noted that patients given iproniazid became cheerful, more optimistic, and more physically active. Soon after its development, iproninazid and related substances were shown to slow enzymatic breakdown of norepinephrine, serotonin and dopamine via inhibition of mitochondrial enzyme monoamine oxidase. For this reason this class of drugs became known as MAOIs. During this time development of distinctively different antidepressant agents was also researched. Imipramine became the first clinically useful TCA. Imipramine was found to affect numerous neurotransmitter systems and to block reuptake of norepinephrine and serotonin from the synapse, therefore increasing the levels of these neurotransmitters. Use of MAOIs and TCAs gave major advances in treatment of depression but their use was limited by unpleasant side effects and significant safety and toxicity issues.[11]
Throughout the 1960s and 1970s the catecholamine hypothesis of emotion and its relation to depression was of wide interest and that the decreased levels of certain neurotransmitters, such as norepinephrine, serotonin, and dopamine might play a role in the pathogenesis of depression. This led to the development of fluoxetine, the first SSRI. The improved safety and tolerability profile of the SSRIs in patients with MDD, compared with TCAs and MAOIs, represented yet another important advance in the treatment of depression.[11]
Since the late 1980s SSRIs have dominated the antidepressant drug market. Today there is increased interest in antidepressant drugs with broader mechanisms of action that may offer improvements in efficacy and fewer adverse effects. In 1993 a new drug was introduced to the US market called venlafaxine, a serotonin-norepinephrine reuptake inhibitor.[12] Venlafaxine was the first compound described in a new class of antidepressive substances called phenylethylamines. These substances are unrelated to TCA and other SSRIs. Venlafaxine blocks the neuronal reuptake of serotonin, noradrenaline, and, to a lesser extent, dopamine in the central nervous system. In contrast with several other antidepressant drugs, venlafaxine can induce a rapid onset of action mainly due to a subsequent norepinephrine reuptake inhibition.[13] See timeline in figure 1.
Timeline of development of antidepressant agents.
Mechanism of action
Monoamines are connected to the pathophysiology of depression. Symptoms are thought to appear because concentrations of neurotransmitters for example norepinephrine and serotonin are insufficient.[14][15] Medications to treat symptoms of depression effect the transmission of serotonin, norepinephrine and/or dopamine.[14] Older and more unselective antidepressants like TCAs and MAOIs, act by inhibiting the reuptake or metabolism, of norepinephrine and/or serotonin in the brain which concludes higher neurotransmitters concentrations.[15] Antidepressants that have dual mechanisms of action, inhibit both serotonin and norepinephrine reuptake, in some cases with weak effect on dopamine reuptake.[14] Antidepressants have effects on variable neuronal receptors like muscarinic-cholinergic, α1- and α2-adrenergic, and H1-histaminergic receptors, and sodium channels in the cardiac muscle, leading to decreased cardiac conduction and cardiotoxicity. Selectivity of antidepressant agents are based on the neurotransmitters that are thought to influence symptoms of depression.[16] Drugs that selectively block the reuptake of serotonin and/or norepinephrine have shown to be effective in treating depression and are better tolerated than TCAs. TCAs have comprehensive effects on various neurotransmitters receptors, which leads to lack of tolerability and increased risk of toxicity [17]
Tricyclic antidepressants
Inhibiting the reuptake transport protein results in increased concentrations of serotonin and norepinephrine in the synaptic clefts, leading to improvement of depression symptoms.
TCAs were the first medications that had dual mechanism of action. The mechanism of action of tricyclic secondary amine antidepressants is only partly understood. TCAs have dual inhibition effects on norepinephrine reuptake transporters and serotonin reuptake transporters. Increased norepinephrine and serotonin concentrations are obtained by inhibiting both of these transporter proteins. TCAs have substantially more affinity for norepinephrine reuptake proteins than the SSRIs. This is because of a formation of secondary amine TCA metabolites.[18][19]
In addition, the TCAs interact with adrenergic receptors. This interaction seems to be critical for increased availability of norepinephrine in or near the synaptic clefts. Actions of imipramine-like tricyclic antidepressants have complex, secondary adaptions to their initial and sustained actions as inhibitors of norepinephrine transport and variable blockade of serotonin transport. Norepinephrine interacts with postsynaptic α- and β-adrenergic receptor subtypes and presynaptic α2-autoreceptors. The α2-receptors include presynaptic autoreceptors which limit the neurophysiological activity of noradrenergic neurons in the central nervous system. Formation of norepinephrine is reduced by autoreceptors through the ratelimiting enzyme tyrosine hydroxylase, by decreasing the expression of cyclic AMP-mediated phosphorylation-activation of the enzyme.[19] α2-receptors also cause decreased intracellular cyclic AMP expression which is resulted in smooth muscle relaxation or decreased secretion.[20] TCAs activate a negative-feedback mechanism through its effects on presynaptic receptor mediation. Probable explanation of effects on decreased neurotransmitter release is that as the receptors activate, inhibition of neurotransmitter release occurs, including suppression of voltage-gated Ca2+ currents and activation of G protein-coupled receptor-operated K+ currents. Repeated exposure of agents with this type of mechanism leads to inhibition of neurotransmitter release. However, repeated administration of TCAs finally results in decreased responses of α2-receptors. This desensitization of these responses may be caused due to increased exposure to the endogen norepinephrine or from prolonged occupation of the norepinephrine transport itself caused by allosteric effect. This adaptation allows the presynaptic synthesis and secration of norepinephrine to return to, or even exceed, normal levels of norepinephrine in the synaptic clefts. Overall inhibition of norepinephrine reuptake induced by TCAs, lead to decreased rates of neuron firing (mediated through α2-autoreceptors), metabolic activity, and release of neurotransmitters.[19]
TCAs do not block dopamine transport but might facilitate dopamine effects indirectly by transport-inhibition of dopamine into noreadrenergic terminals in cerebral cortex.[19] Because of multiple effects on different receptors, TCAs have poor tolerability which could result in adverse effects and increased risk of toxicity.[17]
Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of serotonin and are a widely used group of antidepressants.[21] With increased receptors selectivity compared to TCAs, undesired effects like poor tolerability are avoided.[19] Serotonin is synthesized from an amino acid called L-tryptophan. Active transport system regulates the uptake of tryptophan across the blood–brain barrier. Serotonergic pathways are classified into two main ways in the brain; the ascending projections from the medial and dorsal raphe and the descending projections from the caudal raphe into the spinal cord. The reuptake blocking of SSRIs into the presynaptic terminal results in increased concentration of serotonin in the synaptic cleft, just like the TCAs, but with much less additional effects. Altering the serotonin concentrations to higher levels influence symptoms of anxiety which coexist with depression, leading to improvement of depression symptoms.[21]
Selective norepinephrine reuptake inhibitors
There are two major regions in the brain where noradrenergic neurons are located. These regions are called locus coeruleus and the lateral tegmental. With administration of selective NRIs, neuronal activity in locus coeruleus region is induced because of increased concentration of norepinephrine in the synaptic cleft. This results in activation of α2-adrenoreceptors,[15] as discussed in section 5.1. Assays have shown that selective NRIs have insignificant penchant for muscarinic-cholinergic, α1- and α2-adrenergic or H1-histaminergic receptors.[16]
Dual serotonin and norepinephrine reuptake inhibitors
Agents with dual serotonin and norepinephrine reuptake inhibition (SNRIs) are sometimes called nontricyclic serotonin and norepinephrine reuptake inhibitors. Clinical studies suggest that compounds which increase the concentration in the synaptic cleft of both norepinephrine and serotonin are more successful than single acting agents in the treatment of depression. Dual reuptake inhibitors have low affinity at neuronal receptors of the other neurotransmitters which results in a low adverse effects, compared with the TCAs. Nontricyclic antidepressants have improved potency and onset action acceleration in antidepressant response than SSRI alone, which give the impression that synergism is an efficient property in mediating antidepressant activity. Between the nontricyclic SNRIs there are several important differences that are based on pharmacokinetics, metabolism to active metabolites, inhibition of CYP isoforms, effect of drug-drug interactions and the half-life of the nontricyclic SNRIs.[18][22] Combination of mechanisms of action in a single active agent is an important development in psychopharmacology.[22]
Structure activity relationship (SAR)
Aryloxypropanamine scaffold
Several reuptake inhibitors contain an aryloxypropanamine scaffold. This structural motif has potential for high affinity binding to biogenic amine transports.[22] Drugs containing an aryloxypropanamine scaffold have selectivity profile for norepinephrine and serotonin transporters that depends on the substitution pattern of the aryloxy ring. Selective NRIs contain a substituent in 2’-position of the aryloxy ring but SSRIs contain a substituent in 4’-position of the aryloxy ring. Atomoxetine, nisoxetine and reboxetine all have a substitution group in the 2’-position and are selective NRIs while compounds that have a substitution group in the 4’-position (like fluoxetine and paroxetine) are SSRIs. Duloxetine contains a phenyl group fused at the 2’- and 3’-positions, therefore it has dual selective norepinephrine and serotonin reuptake inhibitory effects and has similar potencies for the both transporters.[23] The nature of the aromatic substituent also has a significant influence on the activity and selectivity of the compounds as inhibitors of the serotonin or the norepinephrine transporters.[22]
Aryloxypropanamine scaffold and agents containing it.
Cycloalkanol ethylamine scaffold
Venlafaxine and desvenlafaxine contain a cycloalkanol ethylamine scaffold. Increasing the electron-withdrawing nature of the aromatic ring provides more potent inhibitory effect of norepinephrine uptake and improves the selectivity for norepinephrine over the serotonin transporter.[23] Effects of chloro, methoxy and trifluoromethyl substituents in the aromatic ring of cycloalkanol ethylamine scaffold were tested. The results showed that the strongest electron-withdrawing m-trifluoromethyl analogue exhibited the most potent inhibitory effect of norepinephrine and the most selectivity over serotonin uptake.[23] WY-46824, a piperazine-containing derivative, has shown norepinephrine and dopamine reuptake inhibition. Further synthesis and testing identified WAY-256805, a potent norepinephrine reuptake inhibitor that exhibited excellent selectivity and was efficacious in animal models of depression, pain, and thermoregulatory dysfunction.[24]
Cycloalkanol ethylamine scaffold and agents containing it.
Milnacipran
Structure of milnacipran.
Milnacipran is structurally different from other SNRIs.[18] The SAR of milnacipran derivatives at transporter level is still largely unclear and is based on in vivo efficacy that was reported in 1987. N-methylation of milnacipran in substituent group R4 and R5 reduces the norepinephrine and serotonin activity.[25] Researches on different secondary amides in substitution groups R6 and R7 showed that π electrons play an important role in the interaction between transporters and ligands. A phenyl group in substituent R6 showed effect on norepinephrine transporters. Substituent groups in R6 and R7 with allylic double bond showed significant improved effect on both norepinephrine and serotonin transporters.[25] Studies have shown that when introducing a 2-methyl group in substituent R3 the potency at norepinephrine and serotonin transporters are almost abolished. Methyl groups in substituent groups R1 and R2 also abolished the potency at norepinephrine and serotonin transporters. Researchers found that replacing one of the ethyl groups of milnacipran with an allyl moiety increases the norepinephrine potency.[26] The pharmacophore of milnacipran derivatives is still largely unclear.[25]
The conformation of milnacipran is an important part of its pharmacophore. Changing the SAR in milnacipran changes the stereochemistry of the compound and affects the norepinephrine and serotonin concentration. Milnacipran is marketed as a racemic mixture. Effects of milnacipran resides in the 1S,2R isomer and substitution of the phenyl group in the 1S,2R isomer has negative impact on norepinephrine concentration.[26] Milnacipran has low molecular weight and low lipophilicity. Because of these properties milnacipran exhibits almost ideal pharmacokinetics in humans such as high bioavailability, low inter-subject variability, limited liver enzyme interaction, moderate tissue distribution and a reasonably long elimination half-life. Milnacipran´s lack of drug-drug interactions via cytochrome P450 enzymes is thought to be an attractive feature because many of the central nervous system drugs are highly lipophilic and are mainly eliminated by liver enzymes.[26]
Future development of SAR
The application of an aryloxypropanamine scaffold has generated a number of potent MAOIs.[27] Before the development of duloxetine, the exploration of aryloxypropanamine SAR resulted in the identification of fluoxetine and atomoxetine. The same motif can be found in reboxetine where it is constrained in a morpholine ring system. Some studies have been made where the oxygen in reboxetine is replaced by sulfur to give arylthiomethyl morpholine. Some of the arylthiomethyl morpholine derivatives maintain potent levels of serotonin and norepinephrine reuptake inhibition. Dual serotonin and norepinephrine reuptake inhibition resides in different enantiomers for arylthiomethyl morpholine scaffold.[28] Possible drug candidates with dual serotonin and norepinephrine reuptake inhibitory activity have also been derived from piperazine, 3-amino-pyrrolidine and benzylamine templates.[29]
Clinical trials
Several studies have shown that antidepressant drugs which have combined serotonergic and noradrenergic activity is more effective than SSRIs in treating MDD. Results showed that serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared to SSRIs in treating MDD [30] and have less side effects.[31] Serotonergic-noradrenergic antidepressant drugs used to treat MDD compared to SSRIs and mirtazapine seem to be less expensive than other drugs for example in the UK. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms.[32]
Data from clinical trials have indicated that SNRIs might have pain relieving properties. The pain perception and transmission in the central nervous system have not been fully elucidated however, extensive data support a role of serotonin and norepinephrine in the modulation of pain. This is also supported by data from clinical trials in humans in which antidepressants have been shown to reduce pain and functional impairment in central and neuropathic pain conditions. This property of SNRIs might be used to reduce doses of other pain relieving medication and lower frequency of limited efficacy, safety and tolerability issues.[33] Clinical research data have shown in patients with GAD that the SNRI duloxetine is significantly more effective than placebo in reducing painful physical symptoms of GAD after short-term and long-term treatment. Findings suggested that painful physical symptoms reoccur with relapsing that indicate a need for ongoing treatment in patients with GAD and concurrent painful physical symptoms.[34]
Current status
Levomilnacipran is the enantiomer of milnacipran. Like milnacipran, levomilnacipran is a selective SNRI. Levomilnacipran is currently under development for the treatment of MDD.[35]
Bicifadine is a SNRI. Bicifadine is being developed for the treatment of acute and chronic pain. Clinical research have shown that bicifadine is effective in the treatment of acute dental pain and bunionectomy pain. Bicifadine has also been reported to be as effective as the standard of care in reducing chronic lower back pain.[36]
Products of SNRIs
| Active ingredient | Product name | Therapeutic use | Binding affinity (Ki nm) |
Structure |
|---|---|---|---|---|
| Venlafaxine | Efexor, Effexor | Treatment of major depressive disorder (MDD), including treatment-resistant cases, generalized anxiety disorder (GAD), chronic pain syndromes [12] | 5-HT:7.8 NE:1920 |
|
| Milnacipran | Savella, Ixel, Dalcipran, Toledomin | Treatment of pain and multiple symptoms associated with fibromyalgia syndrome, treatment of MDD [9] | 5-HT:8.4 NE:22 |
|
| Duloxetine | Cymbalta, Ariclaim, Xeristar, Yentreve | Treatment of MDD and fibromyalgia [14] | 5-HT:0.07 NE:1.2 |
|
| Levomilnacipran | Fetzima | Treatment of MDD in adults | 5-HT:NA NE:NA |
|
| Bicifadine | — | Under development [36] | 5-HT:NA NE:NA |
|
| Desvenlafaxine | Pristiq | Treatment of MDD in adults [5] | 5-HT:NA NE:NA |
|
| Sibutramine | Meridia, Reductil | Treatment of obesity [10] | 5-HT:NA NE:NA |
5-HT: Serotonin - NE: Norepinephrine - D: Dopamine - NA: Not available
Indications
SNRIs are approved for treatment of the following conditions:
- Major depressive disorder (MDD)
- Generalized anxiety disorder (GAD)
- Social anxiety disorder (SAD)
- Panic disorder
- Neuropathic pain
- Fibromyalgia
- Chronic musculoskeletal pain.
Pharmacology
Route of Administration
SNRIs are delivered orally, usually in the form of gel capsules. The drugs themselves are usually a fine crystalline powder that diffuses into the body during digestion.
Dosage
Dosages fluctuate depending on the SNRI used due to varying potencies of the drug in question as well as multiple strengths for each drug.
Mode of Action
The disease for which SNRIs are mostly indicated, Major Depressive Disorder, is thought to be mainly caused by decreased levels of serotonin and norepinephrine in the synaptic cleft, causing erratic signaling. Due to the monoamine hypothesis of depression, which asserts that decreased concentrations of monoamine neurotransmitters leads to depression symptoms, the following relations were determined: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life."[37] SNRIs work by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine. This results in an increase in the extracellular concentrations of serotonin and norepinephrine and, therefore, an increase in neurotransmission. Most SNRIs including venlafaxine, desvenlafaxine, and duloxetine, are several fold more selective for serotonin over norepinephrine, while milnacipran is three times more selective for norepinephrine than serotonin. Elevation of norepinephrine levels is thought to be necessary for an antidepressant to be effective against neuropathic pain, a property shared with the older tricyclic antidepressants (TCAs), but not with the SSRIs.[38]
Main article: Reuptake inhibitor
Recent studies have shown that depression may be linked to increased inflammatory response,[39] thus attempts at finding an additional mechanism for SNRIs have been made. Studies have shown that SNRIs as well as SSRIs have significant anti-inflammatory action on microglia[40] in addition to their effect on serotonin and norepinephrine levels. As such, it is possible that an additional mechanism of these drugs that acts in combination with the previously understood mechanism exist. The implication behind these findings suggests use of SNRIs as potential anti-inflammatories following brain injury or any other disease where swelling of the brain is an issue. However, it should be noted that, regardless of the mechanism, the efficacy of these drugs in treating the diseases for which they have been indicated has been proven, both clinically and in practice.
Pharmacodynamics
Most SNRIs function alongside primary metabolites and secondary metabolites in order to inhibit reuptake of serotonin, norepinepherine, and trace amounts of dopamine. For example, venlafaxine works alongside its primary metabolite O-desmethylvenlafaxine to strongly inhibit serotonin and norepinephrine reuptake in the brain. Recent evidence suggests that dopamine and norepinepherine behave in a cotransportational manner, due to dopamine's inactivation by norepinephrine reuptake in the prefrontal cortex, which largely lacks dopamine transporters. Therefore, SNRIs can increase dopamine neurotransmission in this part of the brain.[41] Furthermore, because SNRIs are extremely selective, they have no measurable effects on unintended systems, such as on monoamine oxidase inhibition.[42] Furthermore, studies have shown that SNRIs as well as SSRIs have significant anti-inflammatory action on microglia[40][43][44][45][46][47]
Pharmacokinetics
The usual half-life of SNRIs is 5 hours, with patients reaching peak effectiveness ~4 hours post ingestion.[43][44][45][46][47]
Contraindications
Due to the effects of increased norepinephrine levels and, therefore, higher Noradrenergic activity, pre-existing hypertension should be controlled before treatment with SNRIs and blood pressure periodically monitored throughout treatment. Duloxetine has also been associated with cases of hepatic failure and should not be prescribed to patients with chronic alcohol use or liver disease. Patients suffering from coronary artery disease should avoid the use of SNRIs. Furthermore, due to some SNRIs' actions on obesity, patients with major eating orders such as anorexia nervosa or bulimia should not be prescribed SNRIs.[43] Duloxetine and milnacipran are also contraindicated in patients with uncontrolled narrow-angle glaucoma, as they have been shown to increase incidence of mydriasis.[46][47]
SNRIs should be taken with caution when using St John's wort, as the combination can lead to the potentially fatal serotonin syndrome.[48] There is also a significant risk when combining SNRIs with dextromethorphan, tramadol, cyclobenzaprine, meperidine/pethidine, and propoxyphene. They should never be taken within 14 days of any other antidepressant, especially with monoamine oxidase inhibitors (MAOIs), as combinations of SNRIs with MAOIs can cause hyperthermia, rigidity, myoclonus, autonomic instability with fluctuating vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.[46]
Side-effects
Because the SNRIs and SSRIs both act similarly to elevate serotonin levels, they subsequently share many of the same side-effects, though to varying degrees. The most common include loss of appetite, weight, and sleep. There may also be drowsiness, dizziness, fatigue, headache, increase in suicidal thoughts, nausea/vomiting, sexual dysfunction, and urinary retention. There are two common sexual side-effects: diminished interest in sex (libido) and difficulty reaching climax (anorgasmia), which are usually somewhat milder with the SNRIs in comparison to the SSRIs. Elevation of norepinephrine levels can sometimes cause anxiety, mildly elevated pulse, and elevated blood pressure. People at risk for hypertension and heart disease should have their blood pressure monitored.[43][44][45][46][47]
Precautions
Starting an SNRI regimen
Due to the extreme changes in noradrenergic activity produced from norepinephrine and serotonin reuptake inhibition, patients that are just starting an SNRI regimen are usually given lower doses than their expected final dosing to allow the body to acclimate to the drug's effects. As the patient continues along at low doses without any side-effects, the dose is incrementally increased until the patient sees improvement in symptoms without detrimental side-effects.[49]
Discontinuation syndrome
As with SSRIs, the abrupt discontinuation of an SNRI usually leads to withdrawal, or "discontinuation syndrome", which could include states of anxiety and other symptoms. Therefore, it is recommended that users seeking to discontinue an SNRI slowly taper the dose under the supervision of a professional. Discontinuation syndrome has been reported to be markedly worse for venlafaxine when compared to other SNRIs. As such, as tramadol is related to venlafaxine, the same conditions apply.[50] This is likely due to venlafaxine's relatively short half-life and therefore rapid clearance upon discontinuation.
Overdose
Causes
Overdosing on SNRIs can be caused by either drug combinations or excessive amounts of the drug itself. These overdoses are extremely dangerous and potentially fatal.[43][44][45][46][47]
Symptoms
Symptoms of SNRI overdose, whether it be a mixed drug interaction or the drug alone, vary in intensity and incidence based on the amount of medicine taken and the individuals sensitivity to SNRI treatment. Possible symptoms are as follows:[46]
- Somnolence
- Coma
- Serotonin syndrome
- Seizures
- Syncope
- Tachycardia
- Hypotension
- Hypertension
- Vomiting
Management
Overdose is usually treated symptomatically, especially in the case of serotonin syndrome, which requires treatment with cyproheptadine and temperature control based on the progression of the serotonin toxicity. Patients are often monitored for vitals and airways cleared to ensure that they are receiving adequate levels of oxygen. Another option is to use activated carbon in the GI tract in order to adsorb excess neurotransmitter.[46] It is important to consider drug interactions when dealing with overdose patients, as separate symptoms can arise.
Comparison to SSRIs
The SNRIs were developed more recently than the SSRIs[date missing] and as a result there are relatively few of them. However, the SNRIs are among the most widely used antidepressants today. In 2009, Cymbalta and Effexor were the 11th- and 12th-most-prescribed branded drugs in the United States. This translates to the 2nd- and 3rd-most-common antidepressants, behind Lexapro (#5), the SSRI escitalopram.[51] In some studies, SNRIs demonstrated slightly higher antidepressant efficacy than the SSRIs (response rates 63.6% versus 59.3%).[52] However, in one study escitalopram had a superior efficacy profile to venlafaxine.[53] The side-effects of SNRIs are reported to be slightly less severe in comparison to the SSRIs as well.[citation needed] One of the major complaints that many users of SSRIs have is the negative sexual side-effects that can be very difficult to treat.[2] Although SNRIs can have similar side-effects, many of them can have the opposite effect of increased libido.[citation needed] Wellbutrin, a norepinephrine-dopamine reuptake inhibitor (NDRI) and Savella, an SNRI, have been reported to increase libido in both men and women, although some studies have contradicted these reports.[3] However, the individuals having reported increased libido also tended to report increased anxiety, heart rate, blood pressure, and other negative effects associated with adrenaline increase.
If a person has an abnormal level of certain neurotransmitters in their brain, it may result in having mood swings or a mood disorder.[54] Serotonin is a neurotransmitter in the brain that is involved with sleep, moods, and emotional states. A slight imbalance of serotonin could result in depression. Norepinephrine is a neurotransmitter that is involved with learning, memory, and physical arousal. Like serotonin, an imbalance of norepinephrine may also result in depression.[55]
See also
- Monoamine reuptake inhibitor
References
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UpToDate Contents
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- 1. セロトニン - ノルエピネフリン再取り込み阻害剤（SNRIs）：薬理学、投与、および副作用 serotonin norepinephrine reuptake inhibitors snris pharmacology administration and side effects
- 2. 成人における単極性うつ病：難治性うつ病の治療 unipolar depression in adults treatment of resistant depression
- 3. Infants with antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)
- 4. 成人における初期治療の効果がない線維筋痛症の治療 treatment of fibromyalgia in adults not responsive to initial therapies
- 5. 全般性不安障害に対する薬物療法 pharmacotherapy for generalized anxiety disorder
English Journal
- VEGF plasma level variations in duloxetine-treated patients with major depression.
- Fornaro M, Rocchi G, Escelsior A, Contini P, Ghio M, Colicchio S, De Berardis D, Amore M, Fornaro P, Martino M.SourceDepartment of Neuroscience, Section of Psychiatry, IRCCS AOU San Martino-IST, Genoa 16100, Italy; Scienze della Formazione, University of Catania, Catania, Italy. Electronic address: Dott.Fornaro@gmail.com.
- Journal of affective disorders.J Affect Disord.2013 Nov;151(2):590-5. doi: 10.1016/j.jad.2013.06.055. Epub 2013 Jul 18.
- BACKGROUND: The vascular endothelial growth factor (VEGF) signaling, which modulates angiogenesis and neurogenesis within the neurovascular unit, might play an important role in the neuro-endocrine-immune (NEI) stress-adaptation system. Recent evidence suggests that VEGF is involved in the pathophys
- PMID 23871390
- Seizures during antidepressant treatment in psychiatric inpatients-results from the transnational pharmacovigilance project "Arzneimittelsicherheit in der Psychiatrie" (AMSP) 1993-2008.
- Köster M, Grohmann R, Engel RR, Nitsche MA, Rüther E, Degner D.Source, Rothstrasse 54, 8057, Zürich, Switzerland, matthiaskoester@hotmail.com.
- Psychopharmacology.Psychopharmacology (Berl).2013 Nov;230(2):191-201. doi: 10.1007/s00213-013-3281-8. Epub 2013 Sep 26.
- RATIONALE: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population.OBJECTIVE: This study investigates seizure rates during AD treatment in
- PMID 24068157
- Antidepressant Class, Age, and the Risk of Deliberate Self-Harm: A Propensity Score Matched Cohort Study of SSRI and SNRI Users in the USA.
- Miller M, Pate V, Swanson SA, Azrael D, White A, Stürmer T.SourceDepartment of Health Policy and Management, Harvard School of Public Health, 677 Huntigton Ave, Boston, MA, 02115, USA, mmiller@hsph.harvard.edu.
- CNS drugs.CNS Drugs.2013 Oct 22. [Epub ahead of print]
- BACKGROUND: The US Food and Drug Administration's meta-analyses of placebo-controlled antidepressant trials found approximately twice the rate of suicidal behaviors among children and adults aged 24 years and younger who were randomized to receive antidepressant medication than among those who were
- PMID 24146116
Japanese Journal
- 疼痛 (特集 高齢者に対する向精神薬療法の工夫)
- 鵜飼 聡
- 精神科 20(2), 149-155, 2012-02
- NAID 40019175650
- 三環系抗うつ薬 (認知症学(下)その解明と治療の最新知見) -- (臨床編)
- 荒井 秀典
- 日本臨床 69 (1012増刊10), 153-156, 2011-12
- NAID 40019127451
Related Links
- これまでのSSRIやSNRI ，三環系のお薬で十分な効果が得られない人など，薬の切り替えを選ぶ医師や，希望する患者さんが増え，日本の医療現場の治療方針として一般的に なると，日本人にとっても万能薬になるかどうかも ...
- SNRI「トレドミン」とはどんなお薬ですか？ 当院では、うつ病、パニック障害などの治療薬として、 パキシル と呼ばれるお薬とを使用していますが、それとは別に トレドミン と呼ばれるお薬を処方することがあります。
Related Pictures
★リンクテーブル★
| 国試過去問 | 「110D041」 |
| リンク元 | 「抗うつ薬」「デュロキセチン」「セロトニン症候群」「睡眠時歯ぎしり」「ミルナシプラン」 |
| 関連記事 | 「SNRIs」「SN」「SNR」 |
「110D041」
- 75歳の女性。物忘れを主訴に夫に連れられて来院した。2年前から物忘れが目立つようになり、何度も同じことを尋ねるようになった。買い物で同じ物を買ってくることがあり、そのことを指摘しても適当にはぐらかすようになった。また料理も簡単なものしか作らなくなり、心配した夫に連れられて受診した。大学卒業後、市役所に勤務し、60歳で定年退職した。その後、地域の婦人会活動を活発に行っていたが、最近は外出することがほとんどない。既往歴に特記すべきことはない。診察時、疎通性は比較的良好であるが、時間と場所の見当識障害がみられる。改訂長谷川式簡易知能評価スケールは11点(30点満点)である。その他の神経学的所見に異常を認めない。血液生化学所見に異常を認めない。頭部MRIで両側海馬の萎縮を認める。
- この患者に対する治療薬として適切なのはどれか。
C
※国試ナビ4※ ［110D040］←［国試_110］→［110D042］
「抗うつ薬」
- 英
- antidepressant, antidepressants
- 関
- 薬理学、そううつ病、精神疾患
作用機序
三環系抗うつ薬 tricyclic antidepressant
- ２つの説がある。
- 1. (急性作用)シナプス前膜におけるノルアドレナリン、セロトニンの再取り込み↓→シナプス間隙における薬剤濃度↑
- 2. (慢性作用)(2週間後)シナプス後膜における受容体の数↓
- 慢性作用はシナプス間隙のノルアドレナリン、セロトニン濃度が上昇した結果、シナプス後膜の受容体が減少したために出現すると考えられる。
抗うつ薬
- 三環系
- 四環系
- 非定型抗うつ薬 atypical agent
副作用
- Adams and s Principles of Neurology, Ninth Edition Allan Ropper p.1474
| 不眠、焦燥 | 鎮静 | 低血圧 | 抗コリン作用 | 消化管症状(嘔吐等) | 性機能低下 | 体重増加 | ||
| 三環系 | アミトリプチリン | ± | 2+ | 2+ | 3+ | ± | ＋ | 2+ |
| 三環系 | ドスレピン | ± | 2+ | 2+ | 2+ | ± | ＋ | 2+ |
| 三環系 | イミプラミン | 2+ | ＋ | 2+ | 2+ | ± | ＋ | 2+ |
| SSRI | フルオキセチン | 2+ | ± | ± | ＋ | 2+ | 2+ | ＋ |
| SSRI | パロキセチン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | セルトラリン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | フルボキサミン | 2+ | ＋ | ± | ± | 2+ | 2+ | ＋ |
| SSRI | シタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | エスシタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SNRI | デシプラミン | ＋ | ± | 2+ | ＋ | ± | ＋ | ＋ |
| SNRI | ノルトリプチリン | ＋ | ＋ | ＋ | ＋ | ± | ＋ | ＋ |
| SNRI | マプロチリン | ＋ | ± | ＋ | ＋ | ± | ＋ | 2+ |
| SNRI | ベンラファキシン | 2+ | ± | ± | ± | 2+ | 2+ | ± |
| SNRI | デュロキセチン | ± | ＋ | ± | ＋ | ＋ | ± | ± |
| NDRI | ブプロピオン | 2+ | ± | ± | ＋ | ＋ | ± | ± |
| MAOI | フェネルジン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | トラニルシプロミン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | イソカルボキサジド | 2+ | ± | 2+ | ＋ | ＋ | 2+ | 2+ |
| MAOI | セレギリン | ＋ | ± | ＋ | ＋ | ＋ | ＋ | ＋ |
| NaSSA | ミルタザピン | ± | 3+ | ＋ | ± | ± | ± | 3+ |
| 非定型 | ネファゾドン | ± | 2+ | ＋ | ＋ | ＋ | ± | ＋ |
| 非定型 | トラゾドン | ± | 3+ | ＋ | ± | ＋ | 2+ | ＋ |
「デュロキセチン」
- 英
- duloxetine
- 化
- 塩酸デュロキセチン duloxetine hydrochloride
- 商
- サインバルタ Cymbalta, Yentreve
- 関
- 抗精神病薬、抗うつ薬、セロトニン・ノルアドレナリン再取り込み阻害薬 SNRI
特徴
構造
作用機序
薬理作用
抗菌スペクトル
動態
適応
- うつ病・うつ状態
- 下記疾患に伴う疼痛：糖尿病性神経障害、線維筋痛症、慢性腰痛症、変形性関節症
用法・用量
- 通常、成人には1日1回朝食後、デュロキセチンとして40mgを経口投与する。投与は1日20mgより開始し、1週間以上の間隔を空けて1日用量として20mgずつ増量する。
- なお、効果不十分な場合には、1日60mgまで増量することができる。
- 減量する場合には1-2週で20mgずつ減量しする。20mgまで到達したら、隔日投与、2日おき投与、3日おき投与と投与間隔を長くしていく。離脱症状（身体症状：しびれ・耳鳴り・めまい・頭痛・吐き気・だるさ。精神症状：イライラ・ソワソワ感・不安・不眠。特徴的な症状：シャンピリ感・ビリビリする）に注意する。
注意
禁忌
- 1. 本剤の成分に対し過敏症の既往歴のある患者
- 2. モノアミン酸化酵素阻害剤(MAOI)を投与中あるいは投与中止後2週間以内の患者
- 3. 高度の肝障害のある患者［肝障害が悪化することがある。また、消失半減期が延長し、本剤の血中濃度が上昇することがある。
- 4. 高度の腎障害のある患者［本剤の血中濃度が上昇することがある。
- 5. コントロール不良の閉塞隅角緑内障の患者［症状が悪化することがある。］
副作用
副作用等発現状況の概要
- うつ病・うつ状態の患者を対象とした国内臨床試験において、安全性評価対象例735例中、副作用（臨床検査値異常変動を含む）は663例（90.2％）に認められた。
- 主なものは、悪心269例（36.6％）、傾眠228例（31.0％）、口渇168例（22.9％）、頭痛154例（21.0％）、便秘102例（13.9％）、下痢87例（11.8％）、めまい80例（10.9％）、トリグリセリド上昇56例（7.6％）、腹部痛52例（7.0％）、ALT（GPT）上昇51例（6.9％）、不眠50例（6.8％）、倦怠感45例（6.1％）、AST（GOT）上昇38例（5.2％）、食欲減退38例（5.2％）であった。（承認時）
重大な副作用
- 1. セロトニン症候群（頻度不明※1）
- 不安、焦燥、興奮、錯乱、発汗、下痢、発熱、高血圧、固縮、頻脈、ミオクローヌス、自律神経不安定等があらわれることがある。セロトニン作用薬との併用時に発現する可能性が高くなるため、特に注意すること。異常が認められた場合には投与を中止し、体冷却、水分補給等の全身管理と共に適切な処置を行うこと。
- 2. 抗利尿ホルモン不適合分泌症候群（SIADH）（頻度不明※1）
- 低ナトリウム血症、低浸透圧血症、尿中ナトリウム排泄量の増加、高張尿、痙攣、意識障害等を伴う抗利尿ホルモン不適合分泌症候群（SIADH）があらわれることがあるので、異常が認められた場合には投与を中止し、水分摂取の制限等適切な処置を行うこと。
- 3. 痙攣（0.27％）、幻覚（頻度不明※1）
- 痙攣、幻覚があらわれることがあるので、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 4. 肝機能障害、肝炎、黄疸（頻度不明※1）
- AST（GOT）、ALT（GPT）、γ-GTP、総ビリルビン等の上昇を伴う肝機能障害、肝炎、黄疸があらわれることがあるので、適宜肝機能検査を行うとともに、患者の症状を十分に観察し、異常が認められた場合には、減量、休薬又は中止するなど適切な処置を行うこと。
- 5. 皮膚粘膜眼症候群（Stevens-Johnson症候群）（頻度不明※1）
- 皮膚粘膜眼症候群（Stevens-Johnson症候群）があらわれることがあるので、観察を十分に行い、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 6. アナフィラキシー反応（頻度不明※1）
- 呼吸困難、痙攣、血管浮腫、蕁麻疹等を伴うアナフィラキシー反応があらわれることがあるので、観察を十分に行い、異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 7. 高血圧クリーゼ（頻度不明※1）
- 高血圧クリーゼがあらわれることがあるので、高血圧又は心疾患のある患者においては血圧の推移等に十分注意しながら投与すること。異常が認められた場合には投与を中止し、適切な処置を行うこと。
- 8. 尿閉（頻度不明※1）
- 尿閉があらわれることがあるので、症状があらわれた場合には投与を中止し、導尿を実施するなど適切な処置を行うこと。
添付文書
http://www.info.pmda.go.jp/go/pack/1179052M1022_2_03/
「セロトニン症候群」
概念
- 抗うつ薬(特に SSRI と呼ばれる選択的セロトニン再取り込み阻害薬。≒セロトニン受容体作動薬)などのセロトニン系の薬物を服用中に出現する副作用
- 精神症状（不安、混乱する、いらいらする、興奮する、動き回るなど）
- 錐体外路症状（手足が勝手に動く、震える、体が固くなるなど）
- 自律神経症状（汗をかく、発熱、下痢、脈が速くなるなど）
- 服薬開始数時間以内に症状が表れることが多い
- 服薬を中止すれば24時間以内に症状は消失
- 「不安」、「混乱する」、「いらいらする」に加えて以下の症状がみられる場合に医療機関受診を推奨している(参考1)
- ｢興奮する｣、「動き回る」、「手足が勝手に動く」、｢眼が勝手に動く｣、｢震える｣、「体が固くなる｣、「汗をかく｣、｢発熱｣、｢下痢｣、「脈が速くなる」
原因となりうる薬剤
トリプトファン、アンフェタミン、コカイン、MDMA、LSD、レボドパ、カルビドパ、トラマドール、ペンタゾシン、メペリジン、SSRI、SNRI、TCA、MAO阻害薬、リネゾリド、5-HT3阻害薬(オンダンセトロン、グラニセトロン)、メトクロプラミド(プリンペラン)、バルプロ酸、カルバマゼピン、シブトラミン(やせ薬)、シクロベンザプリン(中枢性筋弛緩)デキストロメルファン、(メジコン)、ブスピロン(5-HT1A阻害薬、抗不安薬)、トリプタン製剤、エルゴタミン、フェンタニル、リチウム
診断基準
- QJM. 2003 Sep;96(9):635-42
Hunter criteria
感度84%, 特異度97%
- セロトニン作動薬の内服歴と下記の1つ以上
参考
- 1. 重篤副作用疾患別対応マニュアル
「睡眠時歯ぎしり」
- 英
- sleep bruxism
- 関
- 睡眠時ブラキシズム、sleep-related bruxism。覚醒時歯ぎしり wakeful bruxism
- 睡眠時に咀嚼筋の運動が活発になり、歯の食いしばりと歯の摩耗を生じる(いわゆる歯ぎしり)。
- 睡眠時歯ぎしりの有病率は小児期に最も多く、その後年齢とともに次第に減少する。有病率としては子供では15-40%、成人では8-10%といわれている。
- 睡眠障害(閉塞性睡眠時無呼吸、睡眠時随伴症)を有するときに認められやすい。
- リスク因子は閉塞性睡眠時無呼吸(OR 1.8)、アルコール多飲(OR 1.8)、イビキ(OR 1.4)、カフェイン摂取(OR 1.4)、喫煙(OR 1.4)、不安(OR 1.3)、ストレス環境下(OR 1.3)とされている。
- 薬剤により誘発されるものとしても報告がある；アンフェタミン、抗精神病薬、SSRI、SNRI、MDMA
- 精神・神経疾患との関連も報告あり；ダウン症候群、レット症候群、脳性麻痺、注意欠陥多動性障害
- 多くの場合治療の必要はない。
- 小児発症の場合は成長に伴い消失する場合がある。
- 歯の摩耗を伴うような場合には、マウスピースで歯を保護する必要があります。
- 薬物が原因の場合には薬物の調節により改善する場合がある。
- 難治例に対しての薬物療法の報告がなされているが括弧としたものはなさそう；クロナゼパム、ジアゼパムなどのベンゾジアゼピン系薬。アミトリプチリン、ブロモクリプチン、クロニジン、プロプラノロール、レボドパ、トリプトファン
「ミルナシプラン」
- 抗うつ薬。
- セロトニン・ノルアドレナリン再取り込み阻害薬 SNRI
- GOO.437t
特徴
- 効果発現が早く、他薬剤との相互作用が少なく安全
- 高齢者にも使用できる
- 抗コリン作用が少ない ← 三環系抗うつ薬は多い
作用機序
- 神経終末のセロトニンおよびノルアドレナリン再取り込み部位に選択的に結合してそれらの再取り込みを阻害
- シナプスにおけるセロトニン、ノルアドレナリンの濃度を上昇させる
「SNRIs」
[★] セロトニン・ノルアドレナリン再取り込み阻害薬, serotonin-norepinephrine reuptake inhibitors
「SN」
「SNR」
- 関
- See Single nucleotide polymorphism