PAROXETINE IN THE TREATMENT OF POST TRAUMATIC STRESS DISORDER : OUR EXPERIENCES

Posttraumatic stress disorder can develop after individual's exposure or witnessing of life threatening events. It is characterized by three clusters of symptoms. The course of PTSD is often chronic and impedes individual's functioning. Studies of PTSD treatment with paroxetine provide evidence for its efficacy in reducing symptoms and its favorable profile of side-effects. The objective of this work was to determine the efficacy of paroxetine in the treatment of PTSD. The sample consisted of 30 subjects with chronic PTSD. All subjects received treatment with paroxetine in therapeutic dose range for six months. Subjects were assessed prior to therapy and following six months of treatment with paroxetine with the use of following instruments: SCL 90-R, Mississippi Questionnaire, and CGI. The results indicate statistically significant reduction on all subscales of SCL 90-R following six months of treatment, P<0,05. The difference between two assessments with Mississippi Questionnaire was statistically significant, P< 0,05. PTSD rate in our sample was reduced from 100% before treatment to 64% after treatment. Paroxetine was administered in daily dose of 20 mg in 88% of the subjects, and 40 mg in the remaining 12%. Unwanted effects were registered in 16,7% of the subjects and they were mild. Objective improvement was registered in 84% of the sample, and subjective improvement was registered in 80%. Reduction of relapse symptoms was registered in 24% of the subjects. Paroxetine proved to be efficient and safe in treatment of symptoms of PTSD in this study.


Introduction
Post traumatic stress disorder (PTSD) is a psychiatric disorder that can develop subsequent to individual's exposure or witnessing of life-threatening events, such as combat experience, natural disasters, serious accidents, terrorist attacks or interpersonal violence (, ).Individuals suff ering from this disorder frequently develop symptoms such as: reliving the traumatic event, diffi culty falling and staying asleep, frequent nightmares with the content of traumatic events that are subjectively so distressing and cause the individual to wake up with a startle and experience signs of significant autonomous system arousal such as profuse sweating and palpitations.Th ese individuals gradually develop feeling of estrangement form their surroundings, they feel detached from the people who are important to them, they are tensed and irritable, and have exaggerated startle response.Th e symptoms described above can be so intense and distressing and last for long periods, thus leading to signifi cant impairment in functioning of the aff ected individuals.Th e current diagnosis of PTSD adequately addresses the symptom developing in individuals exposed to short or singular traumatic events ().In situations where individuals and groups of people survived exposure to prolonged and repetitive catastrophic stress events that has lasted for months and years, the situation changes substantially.Th is has led to a debate among the leading PTSD researchers about the need for introduction of a new diagnosis, new nosologic entity that will better address and describe the symptoms of long-term traumatization ().
Epidemiological data for the populations lacking the experience of massive traumatization of whole communities as was the case in Bosnia and Herzegovina indicate the following: although  of the population will be exposed in their lifetime to potentially traumatic events that can lead to the development of PTSD, this disorder will be present in the course of the lifetime of , women and  men ().Th ese data from the National Commorbidity Survey (NCS) also indicate substantially high rate of co morbid Axis  psychiatric disorders that occur in , of individuals diagnosed with PTSD.In terms of course and prognosis, this study also provides data indicating the disorder's chronicity:  of individuals developing PTSD recover within a year after the traumatic event, while the remaining  develop chronic PTSD, and one third of the individuals with chronic PTSD will remain symptomatic after  years.Th is explains the extent of the problem that PTSD presents for the public health system.The symptoms of PTSD such as hyper-arousal, intrusive memories, impulsivity and inflexibility present the consequence of the impaired functioning of a number of neurobiological systems that was caused by traumatization.Data from existing research studies have demonstrated the impairment in functioning and decrease in volume of hippocampal formation in chronic PTSD.This is in correlation with cognitive deterioration.Also, the activity of Broca's area is decreased while there is evidence of increased activity of the amygdala, mesencephalon and hypothalamus (, , ).Treatment with selective serotonin reuptake inhibitors (SSRI) normalizes the activity in these areas and leads to reduction in psychological symptoms ().
Psychopharmacological studies of PTSD treatment in current literature describe the efficacy of several groups of psychopharmacological agents (antipsychotic drugs, anti anxiety drugs, antidepressants, mood stabilizers).The largest number of studies describes SSRI drugs as the most effi cacious.Hence this group of drugs presents today the fi rst line of pharmacological treatment of PTSD in the majority of algorithms and guidelines for treatment of PTSD.Paroxetine proved to be safe and effi cacious agent leading to a reduction in all three clusters of symptoms PTSD (reliving, avoidance and hyper-arousal) in the majority of published studies ().Th e objective of this work was to determine the efficacy and safety of paroxetine in the treatment of Post traumatic stress disorder (PTSD).

Subjects and Methods
Th e sample in this study consisted of  adult subjects who have been diagnosed with chronic PTSD.Prior to entering in the study all subjects have signed the informed consent form after the potential side-eff ects of treatment with paroxetine have been explained to them.Th e subjects did not receive fi nancial compensation for being part of this study.Th is research was not sponsored by pharmaceutical industry.
All subjects received treatment with paroxetine in therapeutic dose range in the period of six months.Th e subjects were assessed with the following standardized psychometirc instruments: SCL -R for the registration of psychopathological symptoms, Mississippi Questionnaire for evaluation of PTSD symptoms and Clinical Global Impression Scale for the registration of effi cacy and safety of paroxetine treatment.

Results
SCL  -R SCL  scale measures the severity of symptoms on a scale between  to . Th e results obtained on SCL -R Scale show statistically signifi cant reduction in symptoms on all subscales after six months of treatment with paroxetine, p < ,.Depressive symptoms, interpersonal sensitivity, phobic symptoms, obsessive-compulsive symptoms and paranoid ideation show statistically somewhat less reduction compared with a reduction in anxiety, somatization, psychoticism and hostility.Nevertheless, the reduction on all subscales is statistically signifi cant.(Figure ).

MISSISSIPPI QUESTIONNAIRE FOR PTSD
Reduction in PTSD symptoms is statistically signifi cant.Th e diff erence between three measurements is statistically signifi cant on p<, level of signifi cance (Table ).

Percentage of subjects qualifying for the diagnosis of PTSD:
9 before treatment  9 three months follow-up  9 six months follow-up  Th e percentage of subjects qualifying for the diagnosis of PTSD was reduced from  percent pre-treatment to  percent in three months follow-up, and subsequently to  percent in six months follow-up.
Recommended doses of paroxetine for adults is in the range between  and  mg per day.Th e majority of subjects in this study ( percent) achieved signifi cant improvement with the initial adult dose of  mg a day (Table ).
Adverse eff ects of paroxetine (nausea) were registered in  subjects, they were of mild intensity and required no additional treatment or drug discontinuation (Table ).

Results on the modifi ed CGI (clinical global impression) scale
Objective improvement (the reduction of PTSD symptoms) was registered in  subjects.Subjective improvement was registered in  subjects.Relapse of symptoms was registered in  subjects (Table ).

Discussion
Th e results of this study are congruent with the results of previous research studies indicating the effi cacy and safety of SSRIs in the treatment of PTSD (, ).Th e difference between three measurements on SCL -R Scale indicates a statistically significant reduction of symptoms on all subscales following six months of treatment with paroxetine.Th is agent proved to be very effi cacious, leading to objective improvement in  of the subjects and subjective improvement in  of the subjects in this study.Depressive symptoms, interpersonal sensitiv-

Conclusion
. Th e results of this study indicate a signifi cant level of effi cacy of paroxetine in the treatment of PTSD in this group of subjects..In this study paroxetine proved to be a well tolerated drug that has led to signifi cant reduction in all three PTSD symptom clusters (re-experiencing, avoidance and hyper-arousal)..Our results are congruent with the results of other studies of paroxetine effi cacy and safety in the treatment of PTSD.

TABLE 2 .
Daily dose of paroxetine

TABLE 3 .
Unwanted eff ects of paroxetine treatment

TABLE 4 .
Effi cacy of paroxetine ity, phobic symptoms, obsessive-compulsive symptoms and paranoid ideation showed statistically somewhat less reduction compared with a reduction in anxiety, somatization, psychoticism and hostility.Nevertheless, the reduction on all subscales was statistically signifi cant.Clinical experience and treatment guidelines indicate that the reduction of these symptoms usually requires longer duration of treatment.Nevertheless, the reduction of these symptoms was statistically signifi cant in this study.Total score of PTSD symptoms on Mississippi Scale showed a signifi cant reduction, as well as a reduction in diagnosis of PTSD (caseness) after six months of treatment with paroxetine.Similar results were reported in preexisting studies of other researchers.Adverse eff ects of treatment with paroxetine were recorded in , of the subjects and they were of mild intensity.Th is indicates good tolerability of treatment with paroxetine, this also replicating the results of preexisting research.