治療抵抗性うつ病─報告されているその他の治療
治療抵抗性うつ病の潜在的治療法として実に様々な治療薬が研究されている。使用を支持するエビデンスは少ないが,例外的な状況では試す価値があると考えられる治療戦略の概要を本項の表3.5に示す。これらの処方を行う前に一次文献を吟味すべきである。
表3.5 報告されているその他の治療法(アルファベット順であり,好ましい順ではない)
治療 | コメント |
アマンタジン1 (300mg/日まで) |
データは限定的である |
ayahuasca2, 3 | 有効であるが,専門医のみ使用のこと |
ブプレノルフィン4 (0.8-2mg/日) |
適切なエビデンスが認められるが,明らかな禁忌症がある |
カベルゴリン5 2mg/日 |
データは非常に限られている |
D-サイクロセリン6 1,000mg/日 |
1件の小規模RCTで有用な作用が示された |
デキサメタゾン7, 8 3-4mg/日 |
データは限定的である |
デキストロメトルファン+キニジン9, 10 45mg/10mgを1日2回 |
有望な新規治療法。NDMA受容体拮抗薬。デキストロメトルファンの作用を延長させるために,CYP2D6阻害剤としてキニジンが必要である11 |
葉酸/メチル葉酸12-14 (葉酸2mg/日?) |
おそらく有益であるが,試験の質は低い |
hyoscine15 (スコポラミン)(4mcg/kg 静注) |
大きな効果が迅速に得られるというエビデンスが集積している |
ケトコナゾール16 400-800mg/日 |
ほとんど使用されない。肝毒性のリスクがある |
MAOIとTCAを併用17-19 例:トリミプラミンとphenelzine |
かつてはとても幅広く使用されたが,細心の注意が必要である |
mecamylamine20, 21 10mg/日まで |
1件の予備的研究のみ(n=21) |
ミノサイクリン 200mg/日 |
動物試験22および臨床試験23, 24の複数のメタ解析で肯定的な結果が示されている。双極性うつ病を対象とした最近のRCTでは有効性が示されなかった25 |
モダフィニル26-30 100-400mg/日 |
「うつ病に対する精神刺激薬」の項(本Chapter)を参照 |
naltrexone31, 32 100mg/日 |
オピオイド乱用者以外の患者を対象とした試験は実施されていない |
nemifitide33 40-240mg/日 皮下注 |
1件の予備的研究のみ(n=25) |
ノルトリプチリン±リチウム34-37 | 再び注目されるようになった治療選択肢である |
エストロゲン38 (様々なレジメン) |
データは限定的である |
オメガ-3脂肪酸EPA39 | 通常は抗うつ薬に追加する。効果はおそらく用量依存的であり,EPA含有率60%超で総用量は1g/日未満とすべきである |
ピンドロール30, 40-44 5mgを1日3回,または7.5mgを1日1回 |
忍容性は良好でプライマリケアでも開始することができる。データは主に治療反応に関するものである。治療抵抗性うつ病に関するデータは肯定的なものも否定的なものもある |
プラミペキソール38, 39 0.125-5mg/日 |
1件の質の高いRCTで明確な作用が示された |
psilocybin45 10mg/25mgを隔週で |
有効であるが,専門医のみ使用のこと |
リスペリドン46-51 0.5-3mg/日を抗うつ薬に追加 |
他のSGAと比較してRCTによる確固たる支持が概して少ない |
S-アデノシル-L-メチオニン52-54 400mg/日 筋注,または1,600mg/日 経口 |
治療抵抗性うつ病に関するデータは限定的である コクラン・レビューでは使用が若干支持されている55 |
SSRI+buspirone56, 57 60mg/日まで |
STAR*Dで支持されている 高用量を必要とするが忍容性が低くなる(めまいが多い) |
SSRI+TCA58 | 以前は広く使用されていた |
精神刺激薬: アンフェタミン,メチルフェニデート |
転帰は様々である。「うつ病に対する精神刺激薬」の項(本Chapter)を参照 |
高用量のTCA59 | 以前は広く使用されていた。循環モニタリングが必須である |
テストステロン・ゲル30, 60 | テストステロン値が低い場合は有効である |
tianeptine61, 62 25-50mg/日 |
データベースは小さい。多くの国ではtianeptineは入手できない |
トリプトファン63-66 2-3gを1日3回 |
長い間,有効に利用されている |
ベンラファキシン67-70 200mg/日超 |
プライマリケアでも開始することができる NICE71で推奨されている 悪心および嘔吐。中断反応がよくみられる。血圧モニタリングが必須である |
超高用量のベンラファキシン (600mg/日まで)72 |
上欄を参照。循環モニタリングが必須である |
ベンラファキシン+クロミプラミン静注73 | 循環モニタリングが必須である |
亜鉛74 25mg Zn+/日 |
1件のRCT(n=60)で治療抵抗性うつ病に対して良好な結果が得られている |
ziprasidone75-77 160mg/日まで |
支持するデータは不十分である。抗うつ作用はないと思われる |
注:この他に薬物療法以外の治療法として,様々な心理的アプローチ,反復経頭蓋磁気刺激(rTMS),迷走神経刺激療法,脳深部刺激療法,精神外科的処置等がある。このような治療法は,本書の検討範囲を超えている。
EPA:エイコサペンタエン酸,MAOI:モノアミン酸化酵素阻害薬,RCT:無作為化比較試験,SSRI:選択的セロトニン再取り込み阻害薬,TCA:三環系抗うつ薬
(桐野 創)
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