α-blockers and nightmares PTSD-related
Case report
1 Clin Ter 2013; 164 (2):1-3. doi: 10.7417/CT.2013.1501
On the role of noradrenergic system in PTSD and related sleep disturbances. The use of terazosin in PTSD related nightmares: a case report M. Salviati, M. Pallagrosi, G. Valeriani, C. Carlone, L. Todini, M. Biondi Department of Neurology and Psychiatry, “Sapienza” University, Rome, Italy
Abstract
Case report
In PTSD sleep disorders represent an important symptoms dimension, which is associated with more severe PTSD, and increased risk of relapse. The basic treatment for PTSD in not always associated to an improvement of sleep disturbances and nightmares. Alpha-blockers, and more specifically Prazosin, have shown a specific action on sleep disorders in PTSD. We report the clinical case of a young women with PTSD, who was suffering from severe sleep disorder and distressing nightmare. The patient was treated with Terazosin, a conger of Prazosin, and has shown symptom remission. Further studies on the use of alpha-blokers might reveal new therapeutic options in PTSD. Clin Ter 2013; 164(2):1-3. doi: 10.7417/CT.2013.1501
A female patient referred to our structure received the diagnosis of PTSD. She was experiencing persistent nightmares which deeply affected her sleeping quality and caused important clinical distress. The previous treatments (antipsychotics, sleep inductors, antidepressants) didn’t succeed in symptoms remission, the patient was then admitted to Psychiatric ward. A. is a 27 years old university student. She was experiencing intense and distressing anxiety, which deeply affected her functioning. During psychiatric evaluation she appeared tense, anxiety was remarkably present. Mood was frankly depressed when A. spoke about her symptoms, of which she was really concerned about. She complained about severe sleep problems with difficulties in falling asleep, frequent awakenings connected to the impossibility to fall back asleep, to an extent that she felt extremely tired during the day and had important problems with daily activities. The BPRS (brief psychiatric rating scale) total score was 59, with high scores on anxiety and depression. During admission it was possible to investigate symptoms onset. A. speaks about her late childhood as the “worse years of her life”. When she was 11, she was sexually abused for the first time by “family friends”. She was then abused several times, experiences the patient evokes with frank anxiety and rage. She was too young at that age to confront her abusers, thus she lived these traumas with intense helpless feelings and with a profound sense of assault to her physical integrity. This “traumatic period” was accompanied by familiar problems she lived with important worry and anguish. Her family was part of a religious sect, and was really devoted to this cult. A. was obliged to obey the sect precepts, a system of value which conducted her to social isolation and provoked a sort of “brain-wash” she couldn’t oppose too. While reporting this tremendously stressing life events, the patient sometimes appears absent. When asked, she connects the interlocutor’s impression to her experience of flashbacks, connected to this phase of her life. At night she has nightmares where “strange entities, mean and malicious
Key words: alpha blockers, disorder, nightmares, post-traumatic stress, terazosin
Introduction
Sleep disturbances represent important aspects of different psychiatric disorders, which can affect both psychic and physical health. Insomnia and recurring trauma related nightmares represent an important dimension of PTSD: sleep disturbances can be found in up to 70-87% of patients (1). This compound of symptoms is associated with more severe PTSD, and increases risk of relapse (2). There is also evidence that disturbed sleep predicts development of PTSD in trauma survivors (3). International guidelines (4) recommend SSRI as the choice treatment in PTSD patients. However the improvement in sleeping disturbances is not easily achieved through this kind of therapy, with the only exception being fluvoxamine (5). Benzodiazepines might play an important therapeutic role, but only in short term treatment, because of the likelihood to cause addiction and tolerance. Little outcomes have been achieved with antipsychotics and mood stabilizers (5). Noradrenergic increased function has been linked to nightmares associated to PTSD. Thus, α1-adrenergic receptor blockers have been proposed for the treatment of such symptoms (6).
Correspondence: Dott. Massimo Salviati. Viale dell’Università 30, 00185 Roma, Italia. Tel./Fax: +39.06.4436.2895. E-mail:
[email protected]
Copyright © Società Editrice Universo (SEU)
2 persons, who frighten me, are present”. This dreams are so scary and anxiety provoking to suddenly interrupt her sleep and leave her in a frightened state. A state that persists during the day, with persistent hyperarousal. To confirm the clinical hypothesis of PTSD, we administered the Clinical-Administered PTSD Scale for DSM-IV (CAPS) (7). In lifetime evaluation the patient scored 87, which is compatible with a diagnosis of chronic PTSD with delayed onset. The patient received treatment with Aripiprazole, Sertraline and Clonazepam (30 mg, 50 mg and 2 mg per day). After 3 weeks a clinical improvement was achieved in hyperarousal and anxiety, but no modification in sleep disturbances was present. Other treatments were tried with no benefit (Zolpidem 10 mg, Tradozone 75 mg, Delorazepam 1 mg per day). To asses nightmare related distress, we administered the Nightmare Intervention and Treatment Evaluation (NITE) Scale (8). NITE is a self-report instrument composed of 32 items. The scale has 2 items frequency of nightmares (in
M. Salviati, et al. the last week and in the last month) and 2 subscales that measure different aspects of nightmare distress: nightmare mastery (subscale 1) and nightmare helplessness (subscale 2). Nightmare mastery is related to a sense of control over one’s nightmares or an ability to manage the emotional impact of nightmares. Nightmare helplessness is related to fear, emotional disturbance, and sleep difficulty. The score from each subscale can be analyzed and interpreted separately. Higher scores on subscale 1 indicate a higher sense of mastery over nightmares while higher score on subscale 2 indicate a lessened sense of helplessness. The patient nightmare mastery score (T0) was 33 and the nightmare helplessness score 31 (Fig. 1). We were familiar with the literature concerning the positive therapeutic effects of Prazosin on PTSD related sleep disturbances and nightmares (5). Since the patient distress connected to this symptoms was severe, was compromising her life quality, and all the treatment proposed so far didn’t improve her condition, we wanted to try a different solution. Unfortunately, Prazosin is not available in Italy.
Fig. 1. NITE scale scores at the time T0 (patient before treatment with terazosin), T1 (patient after 4 weeks of treatment with terazosin) and T2 (patient after 6 weeks of discontinuation of therapy with terazosin).
α-blockers and nightmares PTSD-related The other alpha-blocker which is available is Terazosin. As Prazosin, it is an alpha-1-selective adrenoceptor blocking agent, approved for the treatment of symptomatic benign prostatic hyperplasia and hypertension. It has been widely tested for these conditions and tolerability is comparable to Prazosin (9). Terazosin is a Prazosin conger which only differs for the saturation of the furan ring that results in a stronger solubility, and has a half-life that is three to four times longer. We explained the patient the clinical evidence about the use of Prazosin in the treatment of symptoms similar to the ones she was presenting. We informed her that this drug is not available in Italy, but that we could have used, instead, a similar one (Terazosin) which has a similar safety, and action mechanisms. The patient fully understood the information and gave her written and informed consent to the treatment administration. After a week treatment with terazosin (2 mg per day), associated to basic treatment, a reduction in nightmares frequency was observed. A new NITE evaluation was performed 4 weeks after treatment initial administration (T1). A. reported an important decrease in nightmares frequency, less dreaming activity in general, and a global improvement in sleep quality. Awakenings were not present anymore, she felt asleep more easily, also because the fear of nightmares was gone. A. was monitored during admission and drug administration: no side effects, hypotension (which represents a possible side effect of terazosin) or pressure levels alterations were observed or complained. When the patient was discharged the BPRS score was 35. 45 days after discharge, the patient asked for a new evaluation because of the relapse of sleep disturbances, anxiety and nightmares. The patient had suspended Terazosin treatment, under the advice of another specialist not connected to our structure, because its not evidence based clinical efficacy. The new NITE evaluation (T2: a month after treatment suspension, with a total treatment length of 6 week) showed: nightmare mastery score 35, nightmare helplessness score 28, last week nightmare frequency 3-4, last month nightmare frequency 13-15 times/month. Discussion
To our knowledge, this is the first account on the use of terazosin for the treatment of PTSD related nightmares and sleep disturbances. Trauma exposure related sleep disturbances play a specific pathogenic role in PTSD (10) and are connected to worse clinical manifestations, and are often resistant to PTSD treatment (11). In clinical practice benzodiazepines represent a common administered drug, for both anxiety and sleep disturbances, though addiction represents an important risk and evidence based positive outcomes are lacking (12). On the existing link between sleep disturbances and PTSD, we can highlight the following points: 1) trauma exposure can be connected to an alteration in the regulating mechanisms of sleep-awake rhythm; 2) PTSD pathogenesis might partially be related to mecha-
3 nisms connected to sleep physiopathology, and the improvement in this domain might have relevant clinical benefits; 3) To obtain improvement in PTSD related sleep disturbances, specific and adequate treatments are needed. The noradrenergic system plays a central role in the regulation of neurobiological mechanisms associated to PTSD symptoms, in both daily anxiety and sleep disturbances. An increase in noradrenergic function in dangerous situations can lead to over-consolidation of amygdala connected memories (13). The lateral nucleus of the amygdala (LA) has been proven to have an important role in fear conditioning (14). Also alpha1 receptors are gaining attention in the mechanisms of fear conditioning, in fact they are expressed in LA, and it is suggested that alpha1 receptors contribute to inhibition in fear conditioning pathways (15). The α1adrenergic receptor stimulation in CNS breaks sleep physiology, increases nightmares, raises Corticotropin Releasing Factor levels (a mediator connected to anxiety provoking and deep sleep interruption), and it is linked to alarm-related cognitive process (16). Quite interesting are evidence based data concerning the role of the alpha-blocker Prazosin, in this particular framework. In recent literature we found 3 randomized clinical trials, which specifically study sleep disturbance in PTSD and focus on their treatment. Raskind et al. (16) considered the effect of Prazosin on 10 veterans suffering from chronic PTSD resistant to treatment, in a double blind trial with placebo control group. Nightmare severity was significantly improved (p0,01), and REM sleep time (p
