by Johannes G.B.M. Rohlof Revision of an article previous publiced (in Dutch) in the Tijdschrift voor Psychiatrie, 37 (1995), 488-497.

Abstract

There is an increasing number of refugees in Western Europe. Many of them are traumatized by events in the country of their origin and during the flight from that country. Trauma treatment generally consists of psychotherapy (exposure and coping techniques) but often psychotropic drugs are needed. A proper diagnosis is necessary for treatment; often the diagnosis of post-traumatic stress disorder is made, but there is much comorbidity. In non-Western individuals medication should be dosed carefully because of lower effective dose. Often there are also problems with compliance in using the drug. At the moment antidepressants are used in the post-traumatic stress disorder, from the first as well as from the second generation. If the only complaint is of nightmares, longer acting benzodiazepines are recommended as sleeping medication. A good matching of pharmacotherapy and psychotherapy is fundamental if negative interaction is to be prevented.

Introduction

The number of refugees in Western Europe has largely increased in the last decade. In fact a large number of non-Western immigrants in Western Europe consists of refugees. Many of them will stay here because of lasting political problems in their country of origin: Iran, Iraq, Somalia, the former Yougoslavia, and other Asian and African countries. Whether refugees come to Western Europe for political or for other, for instance economical, reasons, is a discussion out of range for this article. Conforming the treatise of Geneva refugees have to be recognised on the basis of their oppression on political or ethnical grounds, but every European country has his own interpretation of these sentences, so that the practice of admission of refugees differs from one country to another. In fact, refugees are often a toy of political debate. We should therefore consider the terms political and economical refugees with great caution. A great part of the refugees has to handle with serious traumatisation: acts of war, imprisonment, torture, oppression, fear of being discovered during their flight, etcetera. This has an impact for mental health care, since coping with traumatic experiences will turn out to be too difficult for many refugees. An expectation is that a lot of refugees will come into psychiatric treatment because of their traumatic experiences. Like we saw with survivors of the terror of the second World War, there is often a delay in the demand for treatment. Therefore we can expect an increased demand in the next years. The psychotherapeutical treatment of patients who experienced traumas consists nowadays of a combination of exposure, individual support and preparing a safe and supportive environment. In exposure, a behavioural technique, the therapist gives the patient the opportunity to talk and to reenact the memories of the trauma in a quiet treatment setting and learns him to cope with intrusions and nightmares. There has been research on methods of psychotherapeutical treatment for trauma victims: exposure seems to be superior to other techniques (Solomon et al., 1992). In a Dutch study three different techniques were studied: psychodynamic treatment, hypnotherapy and desensitisation. All of them gave the same positive outcome (Brom et al, 1989). There are various reasons why the psychiatrist is asked to give a pharmocological treatment for traumatised refugees. In a number of cases there is a possibility for pychotherapeutical treatment, but the patient still has complaints of a poor control of symptoms like depression, lack of sleep and recurrent intrusive memories. Psychotropic drugs can support the psychotherapeutical treatment in these cases. With other patients a psychotherapeutical treatment is (still) not possible. They cannot talk or do not want to talk about their experiences, and have severe complaints of somatic or psychic nature. In some others there is also an insurmountable language problem, by which a psychotherapeutical conversation is not possible. The last reason for pharmacological treatment is the relatively quick recovery reached by psychotropic drugs: in that way patients can be motivated for psychotherapy, which gives only results after a longer period. Next to this, one must recognise the fact that patients often consider recieving medication as being taken serious as a patient. This article is a review of the problems and possibilities of the psychopharmacological treatment of traumatised refugees. There is some literature about medication in traumatised refugees (Vladar Rivero, 1992) but a systematical and updated review is lacking. First we give an overview of the epidemiology. Next there are general remarks about the use of medication by refugees. Then the double-blind randomised studies concerning pharmacological treatment of patients with posttraumatic stress disorder (PTSD) are described. Finally recommendations for clinical practice will follow.

Epidemiology

The posttraumatic stress disorder as described in the DSM-IV (American Psychiatric Association, 1994) is a frequent psychiatric illness, not only in refugees. According to research by Breslau et al. (1990) the lifetime prevalence of PTSD is about 9 %. In an investigation of a large group of refugees (n=480) admitted to a health care institution in the Netherlands Hondius and van Willigen (1992) found a history of torture or prosecution in 92 % of the individuals. Psychic complaints were mentioned by 83 % of this group (n=401); most mentioned were difficulties in sleeping (59 %), fears (47 %), depressive feelings (31 %), disturbances in concentration (28 %), hyperarousal (23 %) and nightmares (19 %) (The sum is higher than 100 % because a number of complaints were mentioned more than once). In a psychiatric admitted group of refugees from Southeast Asia (n=322) Kinzie (1987) found a prevalence of 75 % of PTSD. A complicating factor in PTSD is the comorbidity. In a group of admitted patients with PTSD Davidson et al. (1985) found a concomitant diagnosis of depression in 41 %, of alcohol abuse in 41 %, of bipolar illness in 25 %, and of an anxiety disorder in 19 % of the patients. This troubles not only the interpretation of epidemiological data but also the research on treatment outcome. From the clinical practice a number of considerations can be added. In an individual patient it is hard to estimate the contribution of the traumatisation in the country of origin to the psychiatric symptoms. The present situation of the refugee can also be a great stressor: problems in getting asylum, adaptation to another culture, idleness, the loss of status, identity problems, problems with the family or with countrymen, worries about family members who were left behind, having to deal with racism, etcetera. Many of these stressors can prevent the process of coping of earlier traumata. On the other side: refugees are relatively safe in Western Europe. When somebody has arrived just recently, the lack of language control can be a barrier. When this control has improved a little, it stays sometimes hard to communicate about emotions, since emotions are complicated and abstract topics. Working with interpreters is not always successfull, because of the giant differences between languages: in some languages feelings like depression and anxiety does simply not exist. Next to this, there are cultural hindrances: the meaning and importance of various symptoms can be exaggerated or diminished by patients from other cultures, dependant of the importance in the culture. Examples of this are the frequent complaining of loss of strength and the infrequent report of depression. It may be clear that the process of diagnosing a PTSD in refugees is far from simple. It is obvious that at this moment there is a low report of PTSD: symptoms are often understood to be part of a different syndrom, for instance a somatic syndrom.

Pharmacological treatment: general considerations

When giving medicines to individuals coming from another culture one has to consider a number of things. First, it is the question whether the dosage of medicines have to be the same in individuals coming from different parts of the world. Lin et al. (1986, 1991) offered a review of the literature about the response to medication in different ethnic groups. There are suggestions that particularly Asian patients are favoured by a lower dosage. Reasons for this could be: dietary changes, particularly the carbohydrate-protein ratio, and enzyme deficiencies, of which the most important is the deficiency of acetaldehyde-dehydrogenase, which occurs in 50 % of all Chinese, Japanese and Vietnamese individuals. In non-European individuals antidepressants sooner give clinically effective levels than in Europeans. Till now this was investigated in Asian and in Portorican patients. It seems to be wise to follow the clinical rule to augment very carefully the dosage of antidepressants when given to non-Western individuals. Next to this there is the question of compliance. Two studies showed that the compliance of refugees from Southeast Asia when using antidepressants is very low. Kinzie et al. (1987) found that 61 % of 41 depressive patients had no blood level of antidepressants although these were described. Kroll et al. (1990) found a therapeutic level of antidepressants in only 5 out of 32 patients who claimed to use antidepressive medication: in 10 of the remaining there was a sub-therapeutical level and in 17 no level at all. Kroll et al mentioned a number of factors involved in compliance. One of these is the great sensibility for side effects, while patients have also the tendency to blame the medication for symptoms they already showed before taking the pills, like fatigue, headaches and fears. Furthermore: in developing countries there is an habit to prescibe medicines for a short period, just for symptom reduction. There is also a fear that Western medicines could be too strong or lead to addiction. Kroll et al do also point at the fact that popular belief is sometimes incompatible with the effect of psychotropic drugs: in popular belief some side effects of medication, like a dry mouth or rigidity of the muscles are seen as symptoms of disease. Finally they find in some patients an urge to stay alert and awake. In unsafe areas of the world this could be an essentail tool against evil, but it can also be like this in Europe: the tools to flight are a life-saving quality in many refugees. In families of refugees medicines are used by all members, allthough they are described for one person. The prescibing physician then notices that the pills are used a long time ago; an effective dose is then scarcely reached. From the above mentioned follows that the instructions when prescribing medication for refugees have to be more extended than for the own population. Particularly the side effects have to be looked at. It can be helpful to do an laboratory investigation to the blood level of antidepressants, on the one hand to clarify individual or ethnic differences in pharmacokinetics, on the other hand to control the compliance. The effective levels are well documented for different antidepressants, like amitriptyline, nortriptyline, desipramine and clomipramine, and also for some neuroleptics: haloperidol, flufenazine and perfenazine. For other psychotropic drugs they are reasonably documented (Veefkind et al., 1993).

Pharmacological treatment: criteria of choice for drugs

In the literature there are no articles of randomised, double-blind, placebo-controlled studies for the use of psychotropic drugs in traumatised refugees. There is a limited number of those studies with other persons with PTSD, at the moment six. Solomon et. al (1992) give in a review of the psychopharmacological en psychotherapeutic treatment studies of PTSD an overview. Most studies are concerned with the treatment of traumatised Vietnam veterans. Some studies describe also concencration camp victims and victims of rape. It is important to keep this in mind because, as mentioned, there are differences between groups of patients with PTSD. So, it is important to look which symptoms can be influenced by which medicines. Davidson et al.(1990) performed a controlled study after the influence of amitryptiline in 46 veterans with PTSD. After 8 weeks there was a signifantly better outcome when used amitryptiline compared to placebo. This concerned a total improvement, measured in a number of assessment scales for depression and anxiety and impact of events. There was also an improvement in avoidance symptoms. Reist et al.(1976) did an investigation in 27 admitted veterans with PTSD, whom they treated with desipramine. In this controlled study of 4 weeks they only found a diminishing of depressive symptoms in the desipramine treated group compared to the placebo treated group. Anxiety and PTSD symptoms remained unchanged. Frank et al.(1988) performed a 8 weeks controlled study comparing imipramine, phenelzine (a MAO-inhibitor) and placebo. Imipramine as well as phenelzine proved to work better than placebo on nightmares, intrusive memories, and flashbacks. There was no difference in the effect on avoidance symptoms. The group consisted of 46 veterans. Sheshatzky et al.(1988) found in a study in 13 Israelian patients with PTSD no difference between phenelzine and placebo. Their study lasted 4 weeks. Braun et al.(1990) did an investigation after a benzodiazepine, alprazolam. In their five weeks lasting treatment they found only reduction of anxiety, but no significant changes in depressive symptomatology or PTSD symptoms. Van der Kolk et al. (1994) performed a 5 weeks lasting controlled study with fluoxetine in 64 patients with PTSD, of which 31 were veterans and 33 were otherwise traumatised. The study was followed by an open trial of five months. Fluoxetine appeared to be strongly superior compared to placebo in PTSD symptoms, however something less in the veterans than in the other patients. The symptoms of PTSD in general diminished, and especially the numbing and the hyperarousal. The improvement of all PTSD symptoms is an important finding since the other previous studied agents only had some influence on either the reexperience or the avoidance, but only brought a slight general improvement of all PTSD symptoms, and did not affect the numbing. In general we can state that antidepressants seem to be the psychotropic drugs of choice in the treatment of traumatised patients. In a limited number of cases the only complaint of the traumatised patient is his lack of sleep, often a result of frequent nigtmares. The complaint can be of repeatedly getting awake, not falling asleep or a fear of falling asleep. What should be the pharmacotherapeutical strategy in these cases? At first it is important to complete the diagnostic process: in many patients a PTSD is still present, however covered by other complaints. Psychotherapeutical or pharmacotherapeutical treatment as described before can then be an option. Furthermore it is of interest to look to the coping when waking up after a nightmare. For it is not the nightmare which is the most annoying but the association with really experienced ‘nightmares’: a nocturnal reexperience of a torture gives far more fear than an experience of a persecution in somebody who was never persecuted. Stressing the safety now and strengthening the patient by the thought: I have overcome this misery on my own force, are important therapeutical aspects in coping with these nightmares. In respect to the treatment of nightmares with psychotropic drugs there are no controlled studies to be found in the literature. There are however a number of theoretical concepts. Remembered nightmares mostly occur in REM sleep periods, in which rapid eye movements are prominent (A.Kales et al., 1980). In this respect they can be differentiated from the sleep terrors, which occur with screaming, moving and autonomic disbalance, and often cannot be remembered. Patients who experience a sleep terror are often hard to wake. This disorder is occurring in a non-REM deep sleep stage, in the so-called stages 3 and 4 of the sleep (J.D.Kales et al., 1980). Hypnotics of the benzodiazepine group prolonge in general the REM latency time and diminish the total amount of REM sleep. Also the benzodiazepines shorten the time of the sleep stages 3 and 4. From this theoretical point of view it is to be stated that hypnotics of the bezodiazepine group can diminish nightmares and sleep terrors. However, some notes have to be added. Stopping medication which influences REM sleep after a few weeks can temporarily give a rebound of REM sleep. This fenomenon could be resonsible for the vivid and often unpleasant dreams after stopping benzodiazepine hypnotics. Also, an agent which suppresses REM sleep could be responsible for nightmares in the morning, if it is a short acting hypnotic. Finally, there is the finding of paradoxical stimulation of the nervous system when used benzodiazepines, in which nightmares can occur (Gilman et al., 1990).

Conclusions

If a choice has to be made for a psychotropic drug in the treatment of traumatised patients we have to be rational. At the moment the most rational choice is prescribing an antidepressant. Not only are the antidepressants effective in symptoms of the posttraumatic stress disorder but also in depressions who often come together with PTSD. In some cases where symptoms are limited to nightmares and sleep disturbances, there is a option to choose for a long acting hypnotic of the benzodiazepine group, because of suppresion of REM sleep. Good instruction, careful diminishing and being prepared for paradoxical reactions are important when giving hypnotics. It is obvious that the development of pharmacotherapy in symptoms of traumatisation is still in its infancy. This is however also true for the psychotherapy, about which there is much literature, but very few controlled research (Solomon et al., 1992). New research is also needed of the combination of the two modes, comparable to the research of the combination of psychotherapy and pharmacotherapy in depressions (Weisman, 1979). It is not completely clear wether pharmacotherapy can intensify the effects of the psychological treatment, or that is has a neutral or even a negative influence on psychotherapy. Southwick and Yehuda (1993) hold the view that in a combined pharmacotherapeutical and psychotherapeutical treatment in PTSD the therapist has to monitor his patient very carefully. The therapist has to think of fantasies of being a rescuer, of the symbolic value of medication for the patient as well as the therapist himself, and of the stage of the therapy: stressing medication in the beginning of therapy, stressing psychotherapy later on. Good management of the exact treatment in the exact stage of the therapy is also important for patients from countries where there is another view of the health services: introducing psychotherapeutical methods on time can largely reduce the dependency of the patient. In clinical practice it is important to describe as accurate as possible the course of the disorder and the effects of treatment in traumatised patients. In this way we can learn something of individual treatments. As long as thorough research is lacking, the clinician has to follow his own intuition, combined with the few guidelines described in this article.

Literature

American Psychiatric Association, Diagnostic and statistical manual of mental disorders, fourth edition. A.P.A, Washington D.C., 1994. Braun, P., D.Greenberg, H.Dasberg et al (1990), Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. Journal of Clinical Psychiatry, 51, 236-238. Brom, D., R.J.Kleber and P.B.Defares (1989), Brief psychotherapy for posttraumatic stress disorders, Journal of Consulting and Clinical Psychology, 57, 607-612. Breslau N., G.C.Davis, P.Andreki et al (1990), Traumatic events and posttraumatic stress disorder in an urban population of young adults. Archives of General Psychiatry, 48, 218-222. Davidson, J.R., M.Schwartz, M.Storck et al (1985), A diagnostic and family study of posttraumatic stress disorder. American Journal of Psychiatry. 142, 90-93. Davidson, J, H.Kudler, R.Smith et al (1990), Treatment of posttraumatic stress disorder with amitriptyline and placebo. Archives of General Psychiatry, 47, 259-266. Frank, J.B., T.R.Kosten, E.L.Giller et al (1988), A randomized clinical trial of phenelzine and imipramine for post traumatic stress disorder. American Journal of Psychiatry, 145, 1289-1291. Gilman, A.G., T.W.Rall and A.S.Niess (1990), Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Pergamon, New York, p.349 & 355. Hondius, A.J.K. and L.H.M. van Willigen, Vluchtelingen en gezondheid. Deel II, empirisch onderzoek. Swets & Zeitlinger, Amsterdam, 1992. Kales, A., C.R.Soldatos, A.B.Caldwell et al (1980), Nightmares: clinical charasteristics and personality patterns. American Journal of Psychiatry, 137, 1197-1201. Kales, J.D., A.Kales, C.R.Soldatos et al (1980), Night terrors: clinical characteristics and personality patterns. Archives of General Psychiatry, 37, 1413-1417. Kinzie J.D, P.Leung, J.K.Boehnlein et al (1987), Antidepressant blood levels in Southeast Asians: clinical and cultural implications. Journal of Nervous and Mental Diseases, 175, 480 – 485. Kinzie J.D., J.K.Boehnlein, P.K.Leung et al (1990), The prevalence of posttraumatic stress disorder and its clinical significance among Southeast Asian refugees. American Journal of Psychiatry, 147, 913-917. Kroll J., P.Linde, M.Habenicht et al (1990), Medication compliance, antidepressant blood levels, and side effects in Southeast Asian patients. Journal of Clinical Psychopharmacology, 10, 279-283. Lin, K.M., R.E.Poland and I.M.Lesser (1986), Ethnicity and Psychopharmacology. Culture, Medicine and Psychiatry, 10, 151-165. Lin, K.M. and W.W.Shen (1991), Pharmacotherapy for Southeast Asian psychiatric patients. Journal of Nervous and Mental Diseases, 179, 346-350. Reist, C., C.D.Kaufman and R.J.Haier (1976), A controlled trial of desipramine in 18 men with post-traumatic stress disorder. American Journal of Psychiatry, 146, 513-516. Shehatzky, M., D.Greenberg and B.Lerer (1988), A controlled trial of phenelzine in posttraumatic stress disorder. Psychiatry Research, 24, 149-155. Solomon, S.D., E.T.Gerrity and A.M.Muff (1992), Efficacy of treatments for posttraumatic stress disorder, Journal of the American Medical Association, 268, 633-638. Southwick, S.M. and R.Yehuda (1993), The interaction between pharmacotherapy and psychotherapy in the treatment of posttraumatic stress disorder. American Journal of Psychotherapy, 47, 404-410. Van der Kolk, B.A., D.Dreyfuss, M.Michaels et al (1994), Fluoxetine in post traumatic stress disorder. Journal of Clinical Psychiatry, 55, 517-522. Veefkind, A.H., J.C.L. van Commenée and W.J.Broekema (1993), Serumspiegels van psychofarmaca. Spiegelbeeld, wat vertel je me nou? Tijdschrift voor psychiatrie, 35 , 242-253. Vladar Rivero, V. (1992), The use of psychotropic medication. In: G. van der Veer, Counselling and Therapy with Refugees, Wiley, Chichester, England, p.171-183. Weissman, M.M. (1979), The psychological treatment of depression: Evidence for the efficacy of psychotherapy alone, in comparison with, and in combination with pharmacotherapy. Archives of General Psychiatry, 36, 1261-1269.