Case report
The patient we are reporting on is a 38-year-old woman with an initial presentation of panic attacks for nearly 17 years, previously treated with paroxetine (up to 50 mg once daily) and alprazolam (0.25 mg three times a day) for nearly 1 year with little benefit. Subsequently, she was also treated with citalopram up to 60 mg once daily for nearly 2 years before being referred to a psychiatrist. Her history revealed that she had taken lysergic acid diethylamide (LSD) nearly 17 years ago (at 21 years of age) while she was in the company of her friends and had experienced a ‘bad trip’ at that time. She described being disoriented along with a feeling that the world around her was collapsing and that she was going ‘insane’ during the ‘bad trip’. Furthermore, she also reported ‘dimensions of various objects around her going wrong’ and described symptoms characteristic of derealisation and depersonalisation after taking LSD. She felt that ‘the table was melting into itself’ and ‘her body changing shape’. In addition, she described hitting her head against the wall and being hypervigilant. She reported recovering from symptoms 24 hours later. She denied using ecstasy, cannabis or cocaine during the period immediately before or after the onset of her symptoms.
Although she did not use LSD again, she reported having persistent ‘re-experience phenomena’ characterised by flashbacks to the first ‘bad trip’ for nearly 9 months on a regular basis, after the first ‘bad trip’. An electroencephalogram (EEG) performed nearly 2 years after her LSD use showed no abnormalities, and a CT scan of the brain performed during the same period was also reported as normal by the radiologist (subsequent to a road traffic accident in which she was the driver). For nearly 8 years after her LSD use, she reported having panic attacks that were precipitated by the flashbacks of her first LSD trip. She reported ‘items sinking on her’, but there were no specific environmental triggers to such flashback episodes. Her anxiety attacks were typically reported to last from 30 seconds to a maximum of 1 minute. She denied any dizziness, clumsiness, palpitation, breathlessness, increased sweating, chest pain or vertigo during these episodes. She felt that relaxation breathing exercises did not help her during these episodes of panic attack. Furthermore, no previous history of anxiety disorders or psychotic symptoms before her LSD use was elicited.
Regarding her other drug and alcohol history, she had mild alcohol use disorder (DSM V), drinking up to 19 units of alcohol per night for a maximum of 3 days over the weekend (for nearly 1 year), at the time of presentation to the psychiatrist. In addition, she had a previous history of moderate cannabis use disorder (DSM V), using cannabis as a teenager (from 15 to 17 years of age). However, she denied use of cannabis at initial presentation to the psychiatrist since 17 years of age. She had mild stimulant (cocaine) use disorder (DSM V), using cocaine from 22 to 36 years of age, using them once every 2–4 weeks (snorting 2–3 lines each time) and denied misusing cocaine for the last 2 years. Furthermore, she described mild stimulant (ecstasy) use disorder (DSM V), using ecstasy on a weekly basis in her 20s (once a week up to 2 ecstasy tablets each time). This had later decreased to using 1–2 ecstasy tablets once in every 3–4 weeks and she had last used it nearly 3 years ago. She denied using nicotine or head shop drugs. She denied any significant personal history in her childhood days or school years.
She denied any significant medical history including cardiac problems and was not on any medications other than psychotropics prescribed by her general practitioner (GP). She was initially treated with propranolol up to 80 mg once a day by her GP, with no improvement in symptoms. She continued to feel that ‘the table was melting into itself’ and ‘her body changing shape’. She was also later tried on alprazolam by her GP with little benefit.
Subsequently, she was commenced on risperidone 0.5 mg once daily by the psychiatrist, with significant reduction in the frequency and intensity of the panic attacks and perceptual disturbances within 3–4 weeks. Simultaneously, the dose of her alprazolam was gradually reduced and stopped without any withdrawal effects of the same.
Case discussion
Hallucinogen persisting perception disorder (HPPD) is a disorder that is defined in DSM V as follows [American Psychiatric Association (APA), 2013)].
(a) The re-experiencing following cessation of use of a hallucinogen of one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen (e.g., geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of colour, intensified colours, trial images of moving objects, positive after images, halos around objects, macropsia and micropsia).
(b) The symptoms in criterion (a) cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
(c) The symptoms are not due to a general medical condition (e.g., anatomical lesions and infections of the brain, visual epilepsies) and are not better accounted for by another mental disorder (e.g., delirium, dementia, schizophrenia) or hypnopompic hallucinations.
According to the DSM V criteria, hallucinogens should have been used before the onset of the symptoms, and also the criteria suggest that the symptoms of HPPD persist long after the use of hallucinogens has stopped. Hence, symptoms lasting only days are not considered enough to make a diagnosis of HPPD. Furthermore, it is also necessary to exclude post-traumatic stress disorder, depersonalisation, derealisation, and hallucinogen-induced psychotic mood or anxiety disorders before a diagnosis of HPPD (Halpern & Pope, Reference Halpern and Pope2003).
According to literature, it is prudent not to use the diagnosis of HPPD in cases where current or previous use of an illicit drug may be contributing to the disturbances in perception. Although there have been case reports of alcohol, cannabis or cocaine presenting with HPPD-like symptoms (Batzer et al. Reference Batzer, Ditzler and Brown1999; Gaillard & Borruat, Reference Gaillard and Borruat2003), the person in our case report was not using alcohol, cannabis, cocaine or ecstasy actively (to the extent of substance use disorder) at the time of onset of these symptoms. Furthermore, our patient did not have any similar symptoms when she smoked cannabis in her teenage and did not have her first episode until she used LSD. In addition, the HPPD symptoms were similar to the symptoms experienced during the ‘bad trip’ when she first used LSD. This indicates the use of LSD contributing to the onset of HPPD symptoms. However, the long duration of persistence of these symptoms could be argued as in some way attributed to the mild stimulant (cocaine and ecstasy) use disorders for a prolonged period along with mild alcohol use disorder. It is important to note that most presentations of HPPD symptoms are sub-clinical and resolve by themselves. Case series and reports have reported the duration of HPPD symptoms lasting from 1 day to 3 months (Cooper, Reference Cooper1955; Barron et al. Reference Barron, Lowinger and Ebner1970). Hence, they go undiagnosed and unreported in most cases.
Treatment of HPPD
Treatment of HPPD has been varied and knowledge of treatment has been from case reports. Clonidine has been suggested as a treatment option for patients suffering from LSD-related HPPD on the basis that locus ceruleus and adrenergic activity are suppressed by clonidine. This is based on the hypothesis that post-traumatic stress disorder symptoms such as increased arousal, flashbacks and nightmares are associated with the long-term potentiation of the locus ceruleus pathways to the hippocampus and amygdala (Lerner et al. Reference Lerner, Finkel, Finkel, Oyffe, Merenzon and Sigal1998).
Another case report has also suggested the possibility of the symptoms representing cerebral seizure activity because of variations on the EEG. The patient in that case report has responded to diphenylhydantoin (an antiepileptic medication), with decreased variations on EEG after its use (Thurlow & Girvin, Reference Thurlow and Girvin1971). To support this, a prospective trial demonstrated the efficacy of levetiracetam over a 1-year period in 20 of the 26 patients involved in the study. The same study also reported normalisation of temporal slow patterns on EEG in 23 of the 27 patients after 90 days. Moreover, although EEG abnormalities completely disappeared, flashbacks were reported in 3 of the 27 patients and no patients were reported to have discontinued treatment (Casa & Bosio, Reference Casa and Bosio2005).
Furthermore, a case of psilocybin-induced flashback in a chronic cannabis smoker has been reported and the symptoms have been treated successfully with Sertraline over a 6-month duration (Espiard et al. Reference Espiard, Lecardeur, Abadie, Halbecq and Dollfus2005). In contrast to our case report, there has been a case report suggesting that risperidone might aggravate the symptoms of HPPD. The same authors have reported significant improvement with a combination of fluoxetine and olanzapine (Aldurra & Crayton, Reference Aldurra and Crayton2001). Naltrexone, an opiate receptor blocker has also been shown to be effective in treating the symptoms of HPPD (Lerner et al. Reference Lerner, Oyffe, Isaacs and Mircea1997).
Benzodiazepines are most reported in the treatment of HPPD symptoms with eight of the nine patients responding to benzodiazepines (Abraham, Reference Abraham1983) and both patients responding to clonazepam in another case report (Lerner et al. Reference Lerner, Skladman, Kodesh, Sigal and Shufman2001). There has been another case report in the past describing 5-methoxy-N, N-di-isopropyltryptamine (a hallucinogenic drug with euphoric effects)-induced HPPD symptoms responding to treatment with 1 mg per day of risperidone within a week and no relapse of symptoms later (Ikeda et al. Reference Ikeda, Sekiguchi, Fujita, Yamadera and Koga2005).
Hallucinogens, such as psilocybin, mescaline and LSD, are known to cause perceptual disturbances because of their agonist effect on 5-HT2A receptors (Gonzalez-Maeso & Sealfon Reference Gonzalez-Maeso and Sealfon2006). One hypothesis for the response to risperidone in our case report could be because of the antagonist effect of risperidone on 5-HT2A receptors, even at a lower dose of 0.5–1 mg/day (Talvik-Lofti et al. Reference Talvik-Lofti, Nyberg, Nordstrom, Ito, Halldin, Brunner and Farde2000). The positive response in our patient suggests that risperidone may be effective in other patients with HPPD symptoms. Further research with larger study population would be the best way to examine HPPD and the effective management of its symptoms. However, it may be difficult to recruit a large population with a diagnosis of HPPD. Hence, studies with at least small numbers or more case series would be the best way forward in better understanding HPPD and its management. Moreover, this topic is of increasing relevance because of the emerging pattern of ‘club drugs and legal highs’. Many of these have the potential to cause hallucinations and possibly HPPD symptoms.
Declaration
The authors have not received any remuneration or financial support from anyone for the preparation of this case report.
