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					Use of Topical Application of Lidocaine-
Prilocaine Cream to Reduce Injection-
Site Pain of Depot Antipsychotics
Yuval Bloch, M.D.
Yechiel Levkovitz, M.D.
Alexander Atshuler, M.D.
Vera Dvoretzki, Psych.R.N.
Shmuel Fenning, M.D.
Gideon Ratzoni, M.D.



This study took place in Israel and         tients’ sense of being overly controlled,      Hamilton Rating Scale for Depression
examined the use of a local topical         and the pain or discomfort at the in-          (HAM-D) (8), the Hamilton Rating
anesthetic cream to ameliorate              jection site that some patients experi-        Scale for Anxiety (HAM-A) (9), and
the pain at the injection site              ence (1). A recent study found that the        the Extrapyramidal Symptom Rating
caused by depot antipsychotic               severity of pain that patients experi-         Scale (ESRS) (6). Possible scores on
medications. Fifteen consecutive            enced during an injection was corre-           the CGI range from 1 to 7, with high-
outpatients who had schizophre-             lated with their attitude toward the in-       er scores indicating more severe
nia and who were under treat-               jection (3), and thus depot-associated         symptoms. Possible scores on the
ment with depot antipsychotic               pain might affect patient compliance           BPRS range from 18 to 126, with
medications were enrolled in this           as well.                                       higher scores indicating increased
randomized, double-blind, place-               Lidocaine-prilocaine cream has en-          severity of symptoms. Possible scores
bo-controlled crossover study.              joyed increasing popularity as a local         on the HAM-D range from 0 to 52,
The patients received either lido-          anesthetic to prevent pain from vari-          with higher scores indicating more se-
caine-prilocaine cream or a place-          ous minor medical and surgical proce-          vere depression. Possible scores of the
bo one hour before the injection.           dures, including intramuscular injec-          HAM-A range from 0 to 56, with
The degree of pain at the injec-            tions, without aggravating anticipatory        higher scores indicating more severe
tion site was quantified by the pa-         anxiety (4,5). We explored whether             anxiety. Possible scores on the ESRS
tients’ use of a visual analogue            use of this cream can ease the pain that       range from 0 to 36, with higher scores
scale five minutes after the injec-         is related to depot injections among           indicating more severe extrapyrami-
tion. The application of the lido-          patients with schizophrenia.                   dal symptoms. Patients used a visual
caine-prilocaine cream led to a                                                            analogue scale to quantify their pain at
significant reduction of pain com-          Methods                                        the injection site. The visual analogue
pared with the placebo. (Psychi-            During 1999 a total of 15 consecutive          scale is commonly used in pain studies
atric Services 55:940–941, 2004)            patients from a mental health center           and has been shown to reliably esti-
                                            gave informed consent to participate.          mate quantitative aspects of pain (10).

D     epot antipsychotic medications
      are one way of facilitating and
monitoring medication compliance
                                            Entrance criteria included being an
                                            outpatient, being aged 16 to 65 years,
                                            having a diagnosis of schizophrenia or
                                                                                           The scale ranges from 0 to 10, with 0
                                                                                           representing no pain and 10 repre-
                                                                                           senting maximal (“the most imagina-
among patients with schizophrenia (1),      a schizoaffective disorder from two            ble”) pain.
which reduces relapse rates (2). How-       senior psychiatrists according to                 Injections were given by the same
ever, this type of therapy tends to be      DSM-IV criteria, and being treated             nurse into the gluteus muscle by us-
avoided because of patients’ unsup-         with the same long-acting depot med-           ing a 21 G needle, a .1 air lock, and a
ported fear of more side effects, pa-       ication for at least two months. The           double-needle technique. The Z
                                            study was approved by the institution-         technique was not used.
                                            al Helsinki Committee.                            Participants were randomly as-
The authors are affiliated with the Child      The patients’ clinical condition was        signed to groups by the flipping of a
and Adolescent Outpatient Clinic in Shal-   quantified with the Clinical Global            coin. For the first injection, the pa-
vata, Hod Hasharon, P.O. Box 94, Israel     Impression (CGI) (6), the Brief Psy-           tients were assigned to receive lido-
(e-mail, blochy@netvision.net.il).          chiatric Rating Scale (BPRS) (7), the          caine-prilocaine cream or a placebo
940                                               PSYCHIATRIC SERVICES   ♦ http://ps.psychiatryonline.org ♦ August 2004 Vol. 55 No. 8
one hour before receiving the depot an-        measures demonstrated a significant       the injection after the cream is ap-
tipsychotics in a double-blind, random-        treatment effect (F=20.47, df=1, 13,      plied. In clinical practice this waiting
ized fashion. For the next injection, the      p<.001), indicating that the local        period can be managed by giving pa-
two treatment groups were crossed              anesthetic led to a substantial reduc-    tients the possibility of applying the
over. The placebo was a mineral oil            tion of pain compared with the place-     local anesthetic cream at home, either
cream that is ordinarily used to moisten       bo. The mean score on the visual ana-     by themselves or with the help of
dry skin. Both ointments were pre-             logue scale was .38±.6 for patients       caregivers. The limitations of the
pared on nylon patches, so the nurse           who received the local anesthetic         study include the small sample, the
and examiner were blind to treatment           first, compared with 4.3±3.1 for pa-      short follow-up, and the fact that com-
type. Each patient completed a visual          tients who received the placebo first,    pliance was not monitored. Our study
analogue scale five minutes after each         and .7±.82 for patients who received      was a pilot study. Long-term follow-
injection. A physician (AA) inspected          the local anesthetic second, com-         up studies to monitor how patients’
the area for any local reaction.               pared with 2.2±1.9 for patients who       compliance with depot antipsychotics
   To test the effect of treatment on          received the placebo second. No sig-      is affected by the use of local anes-
pain, a 2 × 2 multivariate analysis of         nificant order effect was seen            thetics are needed to test the clinical
variance with a between-subjects fac-          whether the patient received the local    usefulness of this type of therapy. ♦
tor of order (receipt of placebo first or      anesthetic first or the placebo first,
the local anesthetic first) and a with-        and no order by treatment interaction     Acknowledgment
in-subject factor of treatment (place-         was observed. No significant correla-     The authors thank Gal Gilad, Ph.D., for
bo or local anesthetic) was performed          tions were observed between the in-       his assistance in the statistical analysis.
on visual analogue scale measures.             jected volumes of the depot antipsy-
Correlations were tested with the              chotics and the visual analogue scale     References
Pearson correlation coefficient.               measures after either the placebo or       1. Kane JM, Aguglia E, Altamura AC, et al:
                                                                                             Guidelines for depot antipsychotic treat-
                                               the anesthetic was applied.                   ment in schizophrenia. European Neu-
Results                                           The physician’s impression of the          ropsychopharmacology 8:55–66, 1998
The study sample included 11 males             injected area was that only one sub-       2. Davis JM, Matalon L, Watanabe MD, et al:
(73 percent) and four females (27              ject had mild rubor that resulted from        Depot antipsychotic drugs: place in thera-
percent) whose ages ranged between             the use of the local anesthetic. The          py. Drugs 47:741–773, 1994
23 and 58 years (mean±SD age of                rubor cleared within 30 minutes.           3. Bloch Y, Mendelovic S, Strupinsky S, et al:
42.4±7.9 years). Eleven patients (73                                                         Injections of depot antipsychotics medica-
                                                                                             tions in patients suffering from schizophre-
percent) had a diagnosis of schizo-            Discussion and conclusions                    nia: do they hurt? Journal of Clinical Psy-
phrenia (six had paranoid schizophre-          In this randomized, double-blind              chiatry 62:855–859, 2001
nia and five had unspecified schizo-           placebo-controlled crossover study the     4. Cassidy KL, Reid GJ, McGrath PJ, et al. A
phrenia), and four patients (27 per-           application of a local anesthetic re-         randomized double-blind, placebo-con-
cent) had a diagnosis of schizoaffec-          duced the minor pain at the injection         trolled trial of the EMLA patch for the re-
                                                                                             duction of pain associated with intramuscu-
tive disorder. The range of illness du-        site that was caused by depot antipsy-        lar injection in four to six-year-old children.
ration was four to 28 years (mean of           chotics. This finding is important for        Acta Paediatrica 90:1329–1336, 2001
16.7±6.6 years), and the number of             patients with schizophrenia who are        5. Himelstein BP, Cnaan A, Blackall CS, et al:
hospitalizations ranged from one to14          using depot antipsychotics, who will          Topical application of lidocaine-prilocaine
(mean of 6.3±4.2 hospitalizations).            need repeated injections throughout           (EMLA) cream reduces the pain of intra-
                                                                                             muscular infiltration of saline solution.
   The patients’ medical treatment             long-term therapy. Moreover, because          Journal of Pediatrics 129:718–721, 1996
consisted of haloperidol (two partici-         a considerable number of patients          6. Guy W: ECDEU Assessment Manual for
pants, or 13 percent), fluphenazine            with schizophrenia are characteristi-         Psychopharmacology, Revised. Pub no
(nine participants, or 60 percent), and        cally noncompliant (1), the possibility       ADM 76-338. Rockville, Md, US Depart-
                                                                                             ment of Health, Education and Welfare,
zuclopenthixol (four participants, or          of ameliorating pain from injections          National Institute of Mental Health, 1976
27 percent). The injected volume of            might have a parallel beneficial effect
                                                                                          7. Faustman WO, Overall JW: Brief Psychi-
the antipsychotics ranged from .25 to 4        in enhancing medication compliance.           atric Rating Scale, in The Use of Psycho-
ml (mean of 1.2±.94 ml) and did not            Although our study did not examine            logical Testing for Treatment Planning and
differ among the drugs. The patients’          long-term effect and compliance, the          Outcome Assessment, 2nd ed. Edited by
                                                                                             Maruish M. Mahwah, NJ Lawrence Erl-
mental status on entry to the study in-        fact that one of our previous studies         bawm, 1999
dicated that they were actively psy-           (3) showed a correlation between the
                                                                                          8. Hamilton M: A rating scale for depression.
chotic (mean CGI score of 4±.53 and            pain that patients’ experienced from          Journal of Neurology, Neurosurgery, and
mean BPRS score of 40.9±9.6), that             an injection and their attitude toward        Psychiatry 23:56–62, 1960
they had anxiety and depression (mean          the injection leads one to believe that    9. Hamilton M: The assessment of anxiety
HAM-A score of 11.3±7.6 and mean               the use of a local anesthetic could fa-       states by rating. British Journal of Medical
HAM-D score of 13.7±5.4), and that             cilitate medication compliance. Al-           Psychology 32:50–55, 1959
they had some extrapyramidal side ef-          though there are beneficial effects of    10. Moore A, Moore O, Mcquay H, et al: De-
fects (mean ESRS score of 4.2±3.8).            using a local anesthetic cream, one           riving dichotomous measures from contin-
                                                                                             uous data in randomized controlled trials of
   An analysis of variance that was            should note that there is the incon-          analgesics: use of pain intensity and visual
performed on visual analogue scale             venience of waiting an hour to give           analogue scales. Pain 67:311–315, 1997

PSYCHIATRIC SERVICES   ♦ http://ps.psychiatryonline.org ♦ August 2004 Vol. 55 No. 8                                                    941

				
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