フルオキセチン
**フルオキセチン (Fluoxetine)** は、獣医療において犬や猫のさまざまな行動障害の管理に広く使用されている選択的セロトニン再取り込み阻害薬 (SSRI) の抗うつ薬です。 犬では、行動修正プランと併用して**分離不安**を治療する薬としてFDAに承認されています（商品名：Reconcile®）。また、攻撃性、常同行動（強迫性障害）、全般性不安に対しても適応外で使用されます。猫では、不適切な排泄（尿マーキング）、攻撃性、不安、心因性脱毛/そう痒症に対して頻繁に処方されます。 > **臨床のポイント：** フルオキセチンは、完全な臨床効果が現れるまでに通常 **4〜8週間** のタイムラグが必要です。これはシナプス後受容体のダウンレギュレーションに時間がかかるためです。飼い主には、この初期段階において忍耐強く投薬を続けるよう指導する必要があります。
作用機序: Fluoxetine acts by selectively binding to and inhibiting the presynaptic **serotonin transporter (SERT)** in the central nervous system. * **Inhibition of Reuptake:** Blockade of SERT prevents the reuptake of serotonin (5-HT) into the presynaptic neuron. * **Increased Synaptic Serotonin:** This leads to an accumulation of serotonin in the synaptic cleft → prolonged activation of postsynaptic **5-HT receptors**. * **Receptor Downregulation:** Chronic elevation of synaptic serotonin eventually leads to the downregulation and desensitization of autoreceptors (e.g., 5-HT1A), which correlates with the onset of anxiolytic, anticompulsive, and anti-aggressive clinical effects. Fluoxetine has minimal affinity for other neurotransmitter receptors (such as dopamine, norepinephrine, histamine, or acetylcholine), which accounts for its relatively favorable side effect profile compared to tricyclic antidepressants (TCAs).
動物種別の用量
- Adjunctive treatment of aggression · 0.5-1.5 mg/kg PO once daily · PO · q24h
- To help control urine marking or separation anxiety · 0.5-1 mg/kg (2.55 mg per cat) PO once daily · PO · q24h
- To control pruritus when other therapies have failed · 1-5 mg/cat PO once daily · PO · q24h · Assess therapy after 1-4 weeks. Taper off dose over 6-8 weeks. · Advise obtaining baseline lab work.
- Generalized anxiety disorder · 0.5-1.5 mg/kg PO once daily · PO · q24h
- Urine spraying, psychogenic alopecia, and aggression · 0.5-1.0 mg/kg · PO · q24h · Long-term as directed · Similar precautions for aggression apply as in dogs.
- Treatment of canine separation anxiety in conjunction with a behavior modification plan · 1-2 mg/kg PO once daily · PO · q24h
- Separation anxiety and noise aversions · 1-2 mg/kg PO once daily · PO · q24h · Continue until 2 months after satisfactory response, then discontinue gradually · Use with behavioral therapy. May use long-term. Some dogs require life-long treatment. May add a benzodiazepine during seasonal noise fears.
- Adjunctive pharmacological intervention for conflict-related aggression · 1-2 mg/kg PO once a day · PO · q24h · May take up to 4 weeks for efficacy.
- Compulsive disorders · 1-2 mg/kg PO once daily · PO · q24h
投与経路
禁忌
- Known hypersensitivity to fluoxetine
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs), including selegiline and amitraz (found in some tick collars)
- Patients with epilepsy or a history of seizures
- Concurrent use with drugs that lower the seizure threshold (e.g., acepromazine, chlorpromazine)
- Known sensitivity to fluoxetine or other SSRIs
- History of seizures or epilepsy
有害事象
- Anorexia or decreased appetite (common, often transient)
- Lethargy or depression
- Gastrointestinal upset (vomiting, diarrhea)
- Anxiety, irritability, or restlessness
- Insomnia or hyperactivity
- Panting (dogs)
- Changes in elimination patterns (cats)
- Paradoxical aggressive behavior (in previously unaggressive animals)
- Seizures (rare but possible)
- Lethargy
- Decreased appetite
- Vomiting
- Weight loss
- Trembling
- Restlessness
- Gastrointestinal disturbances
薬物相互作用
- BUSPIRONE · Increased risk for serotonin syndrome
- CYPROHEPTADINE · May decrease or reverse the effects of SSRIs (acts as a serotonin antagonist)
- DIAZEPAM, ALPRAZOLAM · Fluoxetine may increase diazepam and alprazolam plasma levels
- DIURETICS · Increased risk for hyponatremia
- INSULIN · May alter insulin requirements (can alter blood glucose)
- ISONIAZID · Increased risk for serotonin syndrome
- MAO INHIBITORS (e.g., amitraz, selegiline) · High risk for serotonin syndrome; use contraindicated. A 5-week washout is required after stopping fluoxetine before starting an MAOI, and a 2-week washout if switching from an MAOI to fluoxetine.
- PENTAZOCINE · Serotonin syndrome-like adverse effects possible
- PHENYTOIN · Increased plasma levels of phenytoin possible
- PROPRANOLOL, METOPROLOL · Fluoxetine may increase these beta-blocker's plasma levels; atenolol may be safer to use
- TRAMADOL · SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing toxicity risk (serotonin syndrome, seizures)
- TRICYCLIC ANTIDEPRESSANTS (e.g., clomipramine, amitriptyline) · Fluoxetine may increase TCA blood levels and increase the risk for serotonin syndrome
モニタリング
- Efficacy of the behavior modification plan and reduction of clinical signs
- Appetite and body weight (due to risk of anorexia)
- Signs of adverse effects (GI upset, lethargy, paradoxical aggression, seizures)
- Behavioral response and changes in aggression
- Appetite and body weight
- Signs of serotonin syndrome (tremors, agitation, hyperthermia)
- Gastrointestinal tolerance
過量投与
The LD50 for rats is 452 mg/kg. **Clinical Signs of Toxicity:** * **Dogs:** Vomiting, mydriasis (dilated pupils), lethargy, hyperactivity, and seizures. Seizures have been reported at doses twice the highest recommended human dose. * **Cats:** Hypersalivation, vomiting, mydriasis, and excessive vocalization. **Treatment:** * Treatment is symptomatic and supportive. * Gut emptying techniques (emesis, activated charcoal) should be employed if recent and not contraindicated (e.g., patient is seizing or comatose). * **Diazepam** is the treatment of choice for controlling seizures. * **Cyproheptadine** can be administered as a serotonin antagonist if serotonin syndrome is suspected.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。