Posted by Blue Cheer 1 on January 20, 2002, at 10:11:22
In reply to OCD Occurring as a Complication in BZD Withdrawal, posted by Blue Cheer 1 on January 20, 2002, at 9:54:15
This article was published in the _Journal of Nervous and Mental Disease_ 176 (11) :688-691, 1988
> Obsessive-Compulsive Disorder Occurring as a Complication in Benzodiazepine Withdrawal
>
> Lynne M. Drummond, MRCP, MRC.PSYCH., and Helen P. Matthews, MRCGP., DRCOG., MRC.PSYCH.
>
> A case history of obsessive-compulsive disorder occurring in a 32-year-old woman after benzodiazepine withdrawal is presented. The possible biochemical and neuropsychological mechanisms involved in the etiology and maintenance of this condition are reviewed.
> ___________________________________________________________________________________________________________________________________
>
> The precise etiology of obsessive-compulsive disorder remains obscure. Whereas some workers have concentrated on defining neurological abnormalities and propose a neurological model for the development of the disorder (Kettl and Marks, 1986), others have proposed a psychological model (e.g., Hodgson and Rachman, 1972). The psychological vs. biological debate is mirrored in clinical treatment trials in that both psychological treatments (Foa and Goldstein, 1978; Marks et al., 1975, 1980; Baxter, 1985; Insel et al., 1983; Prasad, 1985; Thoren et al., 1980) have been shown to improve symptomatology and alter prognosis. However, in his work on developing a model septo-hippocampal function, Gray (1982) suggests that both neurological and psychological factors may be contributory to the development and maintenance of obsessive-compulsive disorder.
>
> The present case study describes a patient who developed a severe obsessive-compulsive disorder after abruptly stopping benzodiazepine treatment. The authors reported this previously unrecognized complication of diazepam withdrawal elsewhere (Matthews and Drummond, 1987). [Br J Psychiatry 150: 272, 1987]. This paper addresses the theoretical issues raised by the case and reviews Gray's model of septo-hippocamapal function and recent benzodiazepine research.
>
> Case History
>
> Mrs. A., a 32-year-old housewife, had been taking diazepam 6 mg daily for the previous 7 years. She had a history of recurrent episodes of depression and chronic anxiety and had also received intermittent courses of mianserin (10 to 30 mg daily) and amitriptyline (50 mg daily) over this period. There was no history of any symptoms of obsessive-compulsive disorder and no family history of psychiatric disorder. In June 1985, after not receiving antidepressant medication for the preceding 6 months, she abruptly discontinued the diazepam on her general practitioner's advice as she was planning a pregnancy. Two weeks later she developed symptoms of anxiety, hyperacusis, insomnia, and nightmares similar to those described as part of the benzodiazepine withdrawal syndrome (Hallstrom and Lader, 1981; Tyrer et al., 1983). These symptoms persisted for several weeks but were overshadowed by an obsessive-compulsive disorder that developed 4 weeks after discontinuing diazepam.
>
> The central theme of this disorder was her overwhelming fear that she might inadvertently throw away written evidence, which would result in her home and family being removed from her by the authorities. Although she realized that her fear was irrational, she was unable to resist performing a series of checking and avoidance rituals, the prominent features of which included:
>
> a) Repeatedly checking the contents of her trash can.
> b) Repeatedly checking her own and other peoples' clothes, shoes, and money in case they contained written messages.
> c) Hoarding of rubbish in her home and garden and collecting any paper she saw on the road and pavement outside.
> d) Frequently requesting family members and friends to join in her checking rituals and seeking reassurance that no paper had left the home.
> e) Removal of al the paper and writing implements from her home.
> f) Refusal to remain at home, requiring an escort to the toilet and bath to ensure she did not throw papers out the window.
> g) Waking her husband in the night to request him to check in the garden for any letters she could have thrown out of the window while she was asleep.
> h) Avoidance of contact with other people and refusal to go out of the home alone.
>
> Discussion
>
> There has been much recent publicity in the medical and lay press about the withdrawal syndrome that may occur following benzodiazepine administration (Hallstrom and Lader, 1981; Petursson and Lader, 1981; Tyrer et al., 1983. These findings have been directly linked to biochemical changes induced by benzodiazepine drugs in the brain (Hallstrom, 1985).
>
> Putative benzodiazepine receptors have been demonstrated using ligand-binding techniques (Mohler and Okada, 1977; Squires and Braestrup, 1977). These receptors are widely distributed in brain tissue and a high binding of benzodiazepines has been shown in the cerebral cortex. Activation on the benzodiazepine receptor has been shown to facilitate the action of y-aminobutyric acid (GABA, Guidotti et al., 1978). GABA is an inhibitory cental neurotransmitter (Snyder et al., 1977). Withdrawal symptoms following benzodiazepine administration are considered variants of a rebound phenomenon following prolonged nervous system suppression by GABA (Hallstrom, 1985). Tolerance to many benzodiazepine effects has been demonstrated following several days or weeks of use (Aranko et al., 1983; Oswald et al., 1982). Studies in rats suggest that this tolerance may be a result of a reduction in benzodiazepine receptors induced by chronic benzodiazepine administration (Rosenberg and Chiu, 1979).
>
> In the present case we could, therefore, postulate that the prolonged administration of diazepam led to a decrease in benzodiazepine receptors and a reduction in its effect on the central inhibitory transmitter, GABA. Following abrupt discontinuation of diazepine in 1985, Mrs. A developed symptoms of benzodiazepine withdrawal. These symptoms lasted only a few weeks as previously described by other workers (Hallstrom and Lader, 1981; Petursson and Lader, 1981; Tyrer et al., 1983).
>
> The development of her obsessive-compulsive disorder may be best understood by utilizing Gray's model of the role of the septo-hippocampal system in anxiety and the possible effect of anxiolytic agents on this role.
>
>
> In his work, Gray (1982) develops a model of septo-hippocampal system (SHS) has two important and interrelated functions as: a) a checking system or comparator; and b) a control system acting as a behavioral inhibition system. In this model he suggests that the SHS has multiple connections with higher cortical functions; as well as receiving information from sensory structures, it functions as a checking system that constantly compares the actual stimuli and events perceived by an organism in its surroundings with the expected or predicted sitmuli and events (Figure l). However, if there is a discordance between the predicted and actual stimuli, then the SHS moves into its control mode and funtions as a behavioral inhibitor. In other words novel stimuli, signals of punishment or signals of nonreward, activiate the behavioral inhibition system. Activation of this system results in behavioral inhibition, increase in arousal, and increased attention of the organism to its surroundings (Gray, 1971; Figure 2).
> In the past, obsessive-compulsive symptoms have been considered examples of active avoidance (Gray, l971; Hodgson and Rachman, 1972). However, this model does not explain their repetitive nature.
>
> Gray (1982) suggests that in obsessive-compulsive disorder, the SHS becomes oversensitive and labels too many stimuli as "important" and thus leads to persistent searching for those stimuli, i.e., compulsive checking and ritualizing.
>
> According to his model, benzodiazepine drugs as well as other anxiolytic agents act on the SHS by reducing the tendency for mismatch between expected and actual stimuli to be detected and by a reduction in the activity of behavioral inhibition. We might, therefore, hypothesize the benzodiazepine withdrawal might lead to overactivity in the SHS with resultant increased comparator activity.
>
>
> Conclusion
>
> Evidence from recent work on the biochemical action of benzodiazepine in the brain can be incorporated with Gray's (1982) model of septo-hippocampal function to postulate how obsessive-compulsive symptoms may have been precipitated by benzodiazepine withdrawal in the present case.
>
> During the 7 years of benzodiazepine administration, tolerance to diazepam may have led to a reduction in benzodiazepine receptors, thus reducing the effects of the transmitter GABA.
>
> It could be postulated that benzodiazepine withdrawal led to rebound hyperactivity in the brain due to a rapid reduction in GABA activity. This resulted initially in the benzodiazepine withdrawal syndrome. However, obsessive-compulsive symptoms later developed that appear to be directly related to diazepam withdrawal due to their complete disappearance when diazepam was temporarily recommenced. It therefore appears that the resultant overarousal in the patient's septo-hippocampal system led to inappropriate labeling of previously neutral stimuli as threat cues, which resulted in Mrs. A's repetitive checking symptoms.
>
> Behavioral treatment consisting of prolonged exposure in real life to the feared situation combined with self-imposed response prevention resulted in marked improvement in her condition. This does not necessarily imply that psychological mechanisms were the most important in maintaining the condition as we cannot assume that behavioral treatment does not exert an effect on neurochemical receptors.
>
> This case could be explained using a variety of neurochemical or psychological models. However, the value of relating the findings to Gray's model are that this appears consistent with the acute onset of symptoms, the maintenance of the condition, and its subsequent response to treatment. Although there has been considerable animal work supporting Gray's hypothesis, such clinical examples may provide additional evidence.
>
>
> Footnote: This article is summarized in _Obsessive-Compulsive Disorder: Practical Management_ by Michael A. Jenike et al. (editors) in the chapter: "Theories of Etiology"
poster:Blue Cheer 1
thread:90854
URL: http://www.dr-bob.org/babble/20020116/msgs/90855.html