Depot Medication

Three different depot medications are available. These are given by injection either in the hip or upper arm. They can be given intramuscularly or preferably subcutaneously. The person giving the injection should not use an alcohol swab since this increases the pain. The three choices are haloperidol decanote, fluphenazine decanotate and risperidone (Consta). The haloperidol formulation is given every four weeks while the other two are given every two weeks. Extrapyramidal side-effects, especially with haloperidol and fluphenazine, need to be counteracted in many patients with amantidine or benztropine with amantidine preferred.

Medications should always be started out on an oral basis to assure that there are no uncontrollable side-effects. In general, patients do better on depot medications although all studies have not found this.

Depot Medications Better than Oral: In a meta-analysis, the 1-year relapse rate for long-acting depot medication was 27% compared with 42% for patients who received oral medication. In the only study that lasted for 2 years, the risk of relapse decreased substantially in the depot-treated patients, suggesting that risk of noncompliance may be an even more important factor in relapse over extended periods of time. Relapse and rehospitalization: comparing oral and depot antipsychotics. Schooler NR. J Clin Psychiatry. 12/2003;64 Suppl 16:14-7

Risperdal Consta Best at 50 mg Every Two Weeks: Thirteen patients with schizophrenia received injections of 25, 50, or 75 mg of long-acting risperidone every 2 wk. After injections of 25, 50 and 75 mg on day 44 or day 71, D2 receptor occupancy ranged from 25-48%, 59-83% and 62-72%. Steady-state plasma concentrations were maintained for 4-5 wk after the last injection and then declined rapidly. The results indicate that brain D2 receptor occupancy at steady state after injections of long-acting risperidone was in the range found in patients effectively treated with 2-6 mg of oral risperidone. Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Constatrade mark) in patients with schizophrenia. Gefvert O, Eriksson B, et al. University of Uppsala, Sweden. Int J Neuropsychopharmacol. 2005 Mar;8(1):27-36

Risperidone Consta Helpful But Not Impressive: 400 Schizophrenic patients in 41 centers were given risperidone for 1 week and other anti-psychotics were tapered. Then for 12 weeks they received placebo of IM risperidone long-acting (Risperdal Consta) 25, 50, or 75 mg every 2 weeks. Oral risperidone or placebo was continued for first three weeks. Peak plasma levels reached at 4-6 weeks. 50% of 302 risperidone and 69% of 98 placebo patients did not complete with 12 weeks. 17% of risperidone withdrew due to insufficient response and 13% because of side-effect. PANSS decreased 7 points with risperidone vs. 3 points with placebo. 44% of risperidone patients improved vs. 17% of placebo and not dose related although ESP side-effects were 3%, 14%, and 23% for the three dosages. 4# wt gain at highest dose. Kane J, Eerdekens M, Lindenmayer J, et al: Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003;160:1125-32. Johnson & Johnson. Ed: The advantages over placebo would have been greater probably over a longer period of time.

Uncontrolled Study Suggests Traditional Depot Meds Might Not Be Better: The risk of readmission in patients discharged from six State of Maryland inpatient units on clozapine (N = 41), risperidone (N = 149), and olanzapine (N = 103) were compared with those discharged from the two largest state facilities during the same time period on fluphenazine decanoate (N = 59) or haloperidol decanoate (N = 59). One-year readmission risk were 10% for clozapine, 12% for risperidone, and 13% for olanzapine. These risks were not significantly lower than the readmission risk for fluphenazine decanoate (21%) but were significantly lower than haloperidol decanoate (35%). Rehospitalization risk with second-generation and depot antipsychotics. Conley RR, Kelly DL, Love RC, McMahon RP. Ann Clin Psychiatry. 2003 Mar;15(1):23-31. Ed: This was not a randomized study, so it is possible that the decanoate patients were more difficult patients to begin with.

Haloperidol Decanoate Dosage Study: In a DB study, 105 outpatients with schizophrenia were randomly assigned to four different fixed doses of haloperidol decanoate and treated for 1 year or until relapse. The doses used were 25, 50, 100, and 200 mg given intramuscularly once per month. Rates of symptomatic exacerbation were 15% in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg. A multidose study of haloperidol decanoate in the maintenance treatment of schizophrenia. Kane JM, Davis JM, Schooler N, Marder S, Casey D, Brauzer B, Mintz J, Conley R. Am J Psychiatry. 2002 Apr;159(4):554-60. Ed: It would appear that the 50 mg. dosage is the best starting point.

Haloperidol Oral vs. Decanoate Levels: Data suggest that D2-dopamine-receptor occupancy of 50 mg/4 weeks haloperidol decanoate 1 week after injection corresponds to an oral dose of 4.5 mg/day haloperidol. D2-dopamine-receptor occupancy during treatment with haloperidol decanoate. Scherer J, Tatsch K, Albus M, Schwarz J, Mager T, Oertel WH. Eur Arch Psychiatry Clin Neurosci. 1997;247(2):104-6

Patients Like Depot Meds: In a Danish study of 53 chronic schizophrenics, it was found that 60% of the patients viewed depot medication positively, while only 8% viewed it negatively. Only 70% of patients complained about side-effects, even though 94% had scored as having them. Hypokinesia and hyperkinesis were the side-effects least noticed by the patients, but most noticed by the treating physician, while the opposite was the case with psychic side-effects. Subjective experience of treatment, side-effects, mental state and quality of life in chronic schizophrenic out-patients treated with depot neuroleptics. Larsen EB, Gerlach J. Acta Psychiatr Scand. 1996 May;93(5):381-8

No Difference Oral vs. Depot Haloperidol in One Study: An uncontrolled study of 58 patients discharged on oral and 95 on depot haloperidol found no difference in initial clinical variables nor in success as out-patients over a four year period of time. Univ. Texas. Outcome comparison of patients receiving oral or depot neuroleptic medication. Varner RV, Hays JR, Wagner AL, Averill P. Psychol Rep. 2001 Aug;89(1):169-74

Depot Meds: Q6wk Fluphenazine Decanoate Better: A study of 50 schizophrenic patients using a double-blind method treated them with 1cc Q 2 weeks or Q 6 weeks. No difference was found in anti-psychotic control. Carpenter, U Maryland, Am J Psych 3/99;156:412

Depot Meds: Less Leakage Subcutaneously: In a 40 patient study, researchers found 3% of fluphenazine decanoate leaked out with subcutaneous vs. 13% with IM. Says SC preferable. W. Glazer, Yale, J Clin Psychiatry 48:237-9

Depot Meds: Fluphazine Decanoate 6.25 mg = 25 mg Q2wk: Brentwood VA study found no difference, although lower did more poorly. Am J Psychiatry 84;41:815

Fluphenazine Decanoate 11.5 mg Q2week Did Just as Well as 23 mg. Q 2weeks: Half of 37 stable chronic schizophrenics had their maintenance dosage decreased in a DB study gradually. There was no difference in outcome other than slightly fewer side-effects at the lower dose. A double-blind dose-reduction trial of fluphenazine decanoate for chronic, unstable schizophrenic patients. Grady Memorial. Inderbitzin LB, Lewine RR, Scheller-Gilkey G, Swofford CD, Egan GJ, Gloersen BA, Vidanagama BP, Waternaux C. Am J Psychiatry. 1994 Dec;151(12):1753-9

Thomas E. Radecki, M.D., J.D.

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