抗精神病薬の副作用
錐体外路症状
錐体外路症状(EPS):
- 用量に依存する傾向がある。
- EPSが生じる可能性が最も高いのは,高力価FGAであると考えられる。
- その他の抗精神病薬,特にクロザピン,オランザピン,クエチアピン,アリピプラゾールではEPSの発生率はFGAほど高くないが1,いったん生じると持続する可能性がある2。CUtLASSはEPSに関し,FGAとSGAに違いはないと報告していることに注意する3(しかしFGA群のなかではスルピリドが広く使用されていた)。EPSの生じやすさは,遺伝子的に規定されているのかもしれない4。
統合失調症で薬物治療歴のない場合,同様の運動障害が生じる可能性があることに留意する5-7。薬物治療歴のない初回エピソード患者を対象としたある研究では,ジストニアは1%,パーキンソン症状は8%,アカシジアは11%に生じた7。このような場合,パーキンソン症状やその他の運動異常は,認知機能の低下7, 8および長期的な心理社会的機能の不良9に関連する可能性がある。精神病性疾患の診断が確定しているが薬物治療歴のない患者を対象とした研究では,特発性ジスキネジアは9%,パーキンソン症状は17%に生じた10。あるタイプのEPSが生じた患者には,他のタイプのEPSも生じやすい可能性がある11。物質乱用もジストニア,アカシジア,遅発性ジスキネジアのリスクを増加させる12, 13。アルコール乱用はアカシジアと関連するというエビデンスがいくらかある14, 15。
表1.14 起こりやすい錐体外路症状
ジストニア(コントロール不可能な筋れん縮) | 偽性パーキンソニズム (動作緩慢,振戦等) |
アカシジア(不穏)16 | 遅発性ジスキネジア (異常不随意運動) |
|
徴候および症状17 |
全身に起こる筋れん縮
嚥下困難や発語困難が起こる可能性がある。極端な場合は,後弓反張や顎関節脱臼が起こることがある |
偽性パーキンソニズムは抑うつや統合失調症の陰性症状と間違われやすい |
落ち着きのない主観的に不快な状態で,運動欲求や運動強迫を伴う1
アカシジアは精神病性の激越と間違われやすく,また自殺念慮18や他者への攻撃性19と関連する |
様々な運動障害が出現しうる20
口腔や顔面に重度の運動障害が生じると, 発語,摂食,呼吸等が困難になる可能性がある。ストレスがあると症状は増悪する |
評価尺度 | 特異的な評価尺度はなく,一般的なEPS尺度の一部を使用する | Simpson-Angus EPS Rating Scale21 | Barnes Akathisia Rating Scale22 | 異常不随意運動評価尺度23(Abnormal Involuntary Movement Scale:AIMS) |
有病率 |
約10%24。しかし,以下では有病率が高くなる25
ジストニア反応は高齢者では稀である |
約20%26。しかし,以下では有病率が高くなる
|
様々であるが,FGAによる急性アカシジアでは約25%27。SGAではより少ない 個々の抗精神病薬によるアカシジアの相対的なリスクは不明であるが28,発生率が最も低いのはオランザピン,クエチアピン,クロザピンであるというコンセンサスがある29, 30 |
抗精神病薬を服用している患者では1年に5%生じる31。以下に関連して有病率が高くなる32
SGA服用患者の方が発生率は低い33 |
発症時期 | 急性ジストニアは抗精神病薬の投与開始から数時間以内に起こることがある (IM,IVは数分以内で起こりうる) 遅発性ジストニアは投与開始から数ヵ月-数年で生じる |
抗精神病薬の投与開始または増量から数日-数週以内に生じる | 急性アカシジアは抗精神病薬の投与開始または増量から数時間-数週間以内に生じる。数ヵ月程度持続するアカシジアは「慢性アカシジア」と呼ばれる。遅発性アカシジアはさらに長い時間が経ってから起こる傾向があり,抗精神病薬の減量または中止によって増悪する,または誘発される場合がある16 | 数ヵ月-数年で生じる 抗精神病薬の中止により可逆性が認められる患者の割合は不明であるが,ある程度は年齢に依存すると考えられる20 |
治療法 |
症状の程度により抗コリン薬を経口,IM,またはIVで投与する20
|
状況に応じていくつかの選択肢がある
|
上記のいずれの薬剤も,この適応については承認されていない |
|
(長井 信弘)
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