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Keywords:

  • depression;
  • nightmare;
  • oneiroid state;
  • paroxetine

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

We report on rare side effects of paroxetine. A 67-year-old female patient who had been suffering from prolonged depression for over a year but had not received appropriate treatment was administered 20-mg paroxetine daily. However, the patient required hospital admission after 16 days because of behavioural disturbances and delusions that she was being chased by evil persons from a religious group. The delusions were ultimately confirmed to be serial nightmares and an oneiroid state. The nightmares gradually disappeared following discontinuation of paroxetine. The Adverse Drug Reaction Probability Scale showed a score of 6 (probable). Reports on paroxetine-induced nightmares are rare, and there is a possibility that, in this case, parexetine caused the nightmares in association with depression and assumed underlying brain dysfunction due to ageing.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

Selective serotonin reuptake inhibitors (SSRIs) are now the first-line drug for the treatment of depression. SSRIs are relatively safe drugs and are particularly adaptable to treating the elderly. However, they sometimes produce unexpected and occasionally rare side effects.

In this report, we present rare side effects of paroxetine, namely serial nightmares and an oneiroid state. The patient's nightmares were so intense that she temporarily developed an oneiroid state. Her words were affected by these intense nightmares, and her actions in the oneiroid state disguised her mental state as a delusional-hallucinatory state.

This case is important because the side effects we report can confuse the clinical picture. It also contributes to the ongoing interest in the relationship between dreams and psychotic symptoms, which arose in the 19th century and continues to be discussed today.

CASE REPORT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

A 67-year-old woman consulted our clinic for prolonged depression. After she retired from her job at the age of 62, she had spent time enjoying various hobbies. At age 65, she experienced a feeling of emptiness and thereafter her family noticed a clear alteration in her personality: she readily became angry. She continued to complete housework but stopped engaging in her hobbies. She was referred to a physician with an interest in psychosomatic medicine and was diagnosed with depression. Treatment was started, but her condition worsened, until 6 months later she could no longer do housework and 9 months later she was not eating sufficiently and became bedridden. A 6-week period of hospitalization enabled her to eat a little, and she was treated as an outpatient for 1 year without any further improvement. Details of inpatient treatment are unknown, except that sulpiride was administered as the main drug. Sulpiride is available as an antidepressant in Japan.

At this time the patient consulted our clinic. Our initial therapeutic strategy was a sufficient dose of an antidepressant, and we prescribed 20-mg paroxetine daily. After 14 days of taking paroxetine, the patient became cheerful and showed a good appetite. However, the following day she said to her family, ‘Ms A. (who had at one time harassed her at work) brought around evil persons from a religious group’. She changed into mourning dress and left the house saying, ‘I will return to my old workplace’. She wandered the streets and finally went to a police box to get help. After the police took her home, she stayed awake all night and would not eat anything because she believed that the food was poisoned. She was admitted to our hospital on day 16 of paroxetine administration.

On hospital day 1, the patient appeared anxious and was busy looking around. Although she said that she was not worried about the evil persons from the religious group, she continued saying strange things such as ‘I must go and sell soap. Look, here's a lot of soap’ and ‘I saw my funeral. I was burned alive because I killed about six people on the day of my death’. The patient continued to take 20-mg paroxetine daily, and 2-mg flunitrazepam and 25-mg quetiapine were added for insomnia.

From hospital day 2 onward, the patient mainly showed psychomotor inhibition. Because of insufficient efficacy, paroxetine was replaced with 50-mg milnacipran on hospital day 9. The patient's reaction to milnacipran was poor, and 75-mg clomipramine was started instead on day 20. Clomipramine relieved the depression, and her mood and volition improved around day 40. However, clomipramine caused a drug eruption. Finally, 50-mg amoxapine was started on day 54 and proved to be efficacious. Haematological and blood chemistry examinations were normal. Neuroimaging and electroencephalography suggested no organic brain syndrome.

After relief from depression, the patient explained her experiences before and after admission as follows. Before first contacting us, she did not have any dreams because she could not sleep. Around 10 days after starting paroxetine, she began to have nightmares, with feelings of anxiety carrying over into the daytime. The nightmares were vivid and consecutive. The first serial nightmare involved a long dream (lasting 4 days) in which she was burned at the stake. In the nightmare, someone told her that she was going to be taken to a mountain and abandoned, so she must take a hat. There she was burned alive. However, she felt no heat and an alter ego was watching herself burning. She thought, ‘It is good to be burned’ while watching her body become smoke and ascend to heaven.

The second serial nightmare lasted 7 days until hospital day 5 and involved her being pursued. The evil persons from the religious group came to her house to solicit her and her family. She rejected the solicitation, but her son became a group member and she was chased for refusing to join them. She went to a police box to get help and heard her pursuers saying, ‘Get her! Kill her!’ She was driven to a place like a barn, and her son was ordered to kill her. This was an intense and traumatic experience for the patient, and she could remember details of the barn.

This nightmare had several relations with actual events. The episode of going to a police box in this nightmare seems to correspond to the assistance the police gave her the day before hospitalization. A few years earlier, she had rejected an acquaintance's actual solicitation to join a religious group and had felt sorry for the acquaintance. If she had joined the group, the religious group would have made her sell many bars of soap as a funding activity.

These two serial nightmares were vivid, and the patient could clearly remember the scenes. She explained that her dreams from hospital day 6 onward as ‘ordinary dreams’, although they were rather persecutory in nature: the hospital became a raging inferno, and one of the evil persons was dressed as a doctor, obscuring his true nature. She subsequently became unable to remember her dreams from day 12 onward and was discharged on day 145.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES

On initial presentation, the patient appeared to have major depression with delusions. However, the interview with her after relief of the depression indicated serial nightmares and an oneiroid state. From day 10 of paroxetine administration onward, she experienced abnormal dreams in which she was persecuted by a religious group. These nightmares developed into a daydream in which she actually wandered the streets in order to escape from her pursuers before seeking help from the police on the day before hospitalization. Paroxetine was replaced on hospital day 9. The second serial nightmare actually ended on hospital day 5, but her nightmares continued at first as ordinary bad dreams without serial contents, before gradually decreasing in intensity and becoming trivial dreams. On hospital day 9, she still experienced an ordinary, non-serial nightmare. Thus, it appears that the timing of the nightmares were associated with paroxetine administration. The Adverse Drug Reactions Probability Scale showed a score of 6 (probable).1

Sedative hypnotics, beta-blockers, and amphetamines are the therapeutic modalities most frequently associated with nightmares.2 Although it is unclear whether paroxetine tends to induce nightmares, any drugs associated with norepinephrine, serotonin, or dopamin can induce nightmares.3 Indeed, there are a number of reports suggesting the hallucinogenic potential of SSRIs.4–20 A number of patients who have taken SSRIs combined with other neuroactive drugs or have had organic brain dysfunction have presented with hallucinations.4,5,7–10,15–19 Moreover, a few reports have suggested that SSRIs can also induce nightmares. Lepkifker et al. reported fluvoxamine-induced nightmares,21 and Devulder et al. reported nightmares and hallucinations after initiation of tramadol (a weak opioid with effects on adrenergic and serotonergic neurotransmission) with paroxetine and dosulepine hydrochloride.22 However, the effects of paroxetine specifically remains unclear. Parish reported a case of violent dreams diagnosed as REM sleep behaviour disorder associated with paroxetine.23 REM sleep behaviour disorder may well be one of the causes of nightmares, but our patient did not present with abnormal body movements during sleep.

We speculate that, similar to drug-induced hallucinations, paroxetine can induce nightmares in association with other neuroactive drugs or organic brain dysfunction. While the proposed association between psychosis and dreams dates back to Griesinger,24 contemporary neurochemistry findings interestingly point to an association between dreams and hallucinations or delusions.25 However, it is not surprising that disorganization of mental state progresses in the order of nightmares, an oneiroid state, and a delusional-hallucinatory state from the viewpoint of Ey's structural disorganization of consciousness, in which he describes manic-depressive states, depersonalization, delusional hallucinatory states, oneiroid states, and confusion as a continuum.26

It appears that clinical dosage of paroxetine induced in our patient serial nightmares and an oneiroid state, which was seen only on the day before hospitalization. Paroxetine alone rarely induces nightmares and an oneiroid state, but it can do so in combination with other neuroactive drugs or an underlying organic brain dysfunction. In addition, depression itself may have the potential to develop into an oneiriod state according to Ey's concept. Thus, we believe in our case that paroxetine induced nightmares in association with depression and assumed underlying brain dysfunction due to ageing. Pace-Schott et al. suggest that SSRIs suppress dream recall frequency but increase subjective dream intensity, which is compatible with our patient's clinical course.27 Our patient had nightmares that gradually increased in subjective intensity until she could no longer doubt the reality of the nightmares. At the height of the subjective dream intensity, the nightmare penetrated into daytime wakefulness and manifested as an oneiroid state.

Paroxetine-induced hallucinations and nightmares are a rare but serious side effect. Not only can they be painful for the patient, but they can also alter the clinical picture of depression and confuse clinical thinking.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORT
  5. DISCUSSION
  6. REFERENCES