Davis J M, Matalon L, Watanabe M D, Blake L, Metalon L [corrected to Matalon L ]
Department of Psychiatry, University of Illinois, Chicago.
Drugs. 1994 May;47(5):741-73. doi: 10.2165/00003495-199447050-00004.
The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals of from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. Unfortunately, patients who do not reliably take their oral medications are unlikely to volunteer for controlled studies. This is because the same factors that influence a patient to not cooperate with the physician in taking the medication as prescribed will also interfere with their willingness to volunteer for research protocols. Thus, evidence from blinded controlled trials may not necessarily reflect the actual patient population at risk. We feel that particularly important evidence of efficacy of depot vs oral medication comes from mirror-image studies. In these trials, the number of hospitalisations after initiation of depot medication is compared with that observed when the patient was solely taking oral medication. Studies of this type show that depot medication substantially reduces the rate of relapse. There is considerable evidence about how long depot medications should be used. For many patients, depot medication to prevent relapse in schizophrenia should be used for the life of the patient. As the conventional antipsychotic agents are replaced by a new generation of agents, the need for depot formulations will continue, and the knowledge gained about the current formulations should transfer to future generations of drugs.
长效抗精神病药物的药代动力学特点是,每隔1至4周进行一次肌肉注射会产生足够的血浆浓度,足以在给药间隔期预防复发。这类药物对不能可靠服用口服药的患者有用。抗精神病药物各种长效制剂的药代动力学和临床作用已得到广泛研究。不幸的是,不能可靠服用口服药的患者不太可能自愿参加对照研究。这是因为那些影响患者不按医嘱配合医生服药的因素,也会干扰他们参与研究方案的意愿。因此,来自双盲对照试验的证据不一定能反映实际的高危患者群体。我们认为,长效药物与口服药物疗效对比的特别重要的证据来自镜像研究。在这些试验中,将开始使用长效药物后的住院次数与患者仅服用口服药时观察到的住院次数进行比较。这类研究表明,长效药物可大幅降低复发率。关于长效药物应使用多长时间有相当多的证据。对许多患者来说,预防精神分裂症复发的长效药物应在患者的一生中使用。随着传统抗精神病药物被新一代药物取代,对长效制剂的需求将持续存在,并且从当前制剂中获得的知识应传承给下一代药物。