Posthallucinogen-Like Visual Illusions (Palinopsia) with Risperidone in a Patient without Previous Hallucinogen Exposure: Possible Relation to Serotonin 5HT2a Receptor Blockade

Background: Previous reports document visual illusions resembling hallucinogen persisting perception disorder (HPPD) after risperidone treatment in patients with histories of previous LSD exposure. Methods: We report a case with visual disturbances resembling HPPD after each of three consecutive risperidone dose increases. Results: Contrasting with previous reports, our patient lacked any history of substance abuse, particularly hallucinogen exposure. She lacked neurologic or other contributory illnesses. Illusions generally remitted within 48 hours each time. Coadministration of trazodone and clonazepam may have contributed to these phenomena, although clonazepam has been used to treat this condition. She had been unusually sensitive to the side-effects of many psychotropics. Conclusions: This case is unique due to the absence of substance abuse. This and another report note heightened sensitivity to medication side-effects. Visual phenomena resembling HPPD evidently can occur with risperidone and, possibly, other atypical antipsychotics and certain antidepressants regardless of previous hallucinogen use. Several lines of evidence implicate reduced 5HT2a serotonin receptor stimulation rather than increased 5HT2c stimulation.

References

• 1 Abraham H D. Visual phenomenology of the LSD flashback.  Arch. Gen. Psychiatry. 1983;  40 884-889
• 2 Abraham H D. Visual hallucinations in macular degeneration.  Am. J. Psychiatry. 1993;  150 1758
• 3 Abraham H D, Mamen A. LSD-like panic from risperidone in post-LSD visual disorder.  J. Clin. Psychopharmacol.. 1996;  16 238-241
• 4 Aghajanian G K. Serotonin and the action of LSD in the brain.  Psychiatr. Ann.. 1994;  24 137-141
• 5 Almaula N, Ebersole B J, Ballesteros J A, Weinstein H, Sealfon S C. Contribution of a helix 5 locus to selectivity of hallucinogenic and nonhallucinogenic ligands for the human 5-hydroxytrytamine2A and 5-hydroxytryptamine2C receptors: direct and indirect effects on ligand affinity mediated by the same locus.  Mol. Pharmacol.. 1996;  50 34-42
• 6 Callahan P M, Cunningham K A. Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP).   Eur. J. Pharmacol.. 1994;  257 27-38
• 7 Canton H, Verriele L, Millan M J. Competitive antagonism of serotonin (5-HT)2C and 5-HT2A receptor-mediated phosphoinositide (PI) turnover by clozapine in the rat: a comparison to other antipsychotics.  Neurosci. Lett.. 1994;  181 65-68
• 8 Geller T J, Bellur S N. Peduncular hallucinosis: magnetic resonance imaging confirmation of mesencephalic infarction during life.  Ann. Neurol.. 1987;  21 602-604
• 9 Giannangeli G, Cazzolla N, Luparini M R, Magnani M, Mabilia M, Picconi G, Tomaselli M, Baiocchi L. Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT2A and alpha1 receptor binding affinity.  J. Med. Chem.. 1999;  42 336-345
• 10 Glennon R A. Do classical hallucinogens act as 5-HT2 agonists or antagonists?.  Neuropsychopharmacology. 1990;  3 509-517
• 11 Green K L, Grant K A. Evidence for overshadowing by components of the heterogeneous discriminative stimulus effects of ethanol.  Drug Alcohol. Depend.. 1998;  52 149-159
• 12 Hedges D W, Reimherr F W, Strong R E, Halls C H, Rust C. An open trial of nefazodone in adult patients with generalized anxiety disorder.  Psychopharmacol. Bull.. 1996;  32 671-676
• 13 Hughes M S, Lessell S. Trazodone-induced palinopsia.  Arch. Ophthalmol.. 1990;  108 399-400
• 14 Jenck F, Moreau J L, Berendsen H H, Boes M, Broekkamp C L, Martin J R, Wichmann J, Van Delft A M. Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats.  Eur. Neuropsychopharmacol.. 1998;  8 161-168
• 15 Kawasaki A, Purvin V. Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD).  Arch. Ophthalmol.. 1996;  114 47-50
• 16 Kolmel H W. Peduncular hallucinations.  J. Neurol.. 1991;  238 457-459
• 17 Kraus R P. Visual “trails” with nefazodone treatment.  Am. J. Psychiatry. 1996;  153 1365-1366
• 18 Lauterbach E C, Spears T E. Long-term psychiatric and neurologic treatment after a traumatic midbrain lesion.  Neurocase.. 1997;  3 98-103
• 19 Lima L, Salazar M, Trejo E. Modulation of 5HT1A receptors in the hippocampus and the raphe area of rats treated with clonazepam.  Prog Neuropsychopharmacol Biol Psychiatry. 1993;  17 663-677
• 20 Lima L, Trejo E, Urbina M. Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in the hippocampus of rats subchronically treated with clonazepam.  Neuropharmacology. 1995;  34 1327-1333
• 21 Marek G J, Aghajanian G K. LSD and the phenethylamine hallucinogen DOI are potent partial agonists at 5-HT2a receptors on interneurons in rat piriform cortex.  J. Pharmacol. Exp. Ther.. 1996;  278 1373-1382
• 22 Morehead D B. Exacerbation of hallucinogen - persisting perception disorder with risperidone.  J. Clin. Psychopharmacol.. 1997;  17 327-328
• 23 Moser P C, Redfern P H. The effect of benzodiazepines on the 5-HT agonist-induced head-twitch response in mice.  Eur. J. Pharmacol. 1988;  151 223-231
• 24 Newton R A, Phipps S L, Flanigan T P, Newberry N R, Carey J E, Kumar C, McDonald B, Chen C, Elliott J M. Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.  J. Neurochem.. 1996;  67 2521-2531
• 25 Nyberg S, Farde L, Eriksson L, Halldin C, Eriksson B. 5-HT2 and D2 receptor occupancy in the living human brain. A PET study with risperidone.  Psychopharmacology (Berl.). 1993;  110 265-272
• 26 Sanders-Bush E, Burris K D, Knoth K. Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis.  J. Pharmacol. Exp. Ther.. 1988;  246 924-928
• 27 Schotte A, Janssen P F, Gommeren W, Luyten W H, Van Gompel P, Lesage A S, De Loore K, Leysen J E. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.  Psychopharmacology (Berl.). 1996;  124 57-73
• 28 Schwartz K. Nefazodone and visual side effects.  Am. J. Psychiatry. 1997;  154 1038
• 29 Takeuchi H, Yatsugi S, Hatanaka K, Nakato K, Hattori H, Sonoda R, Koshiya K, Fujii M, Yamaguchi T. Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity.  Eur. J. Pharmacol.. 1997;  329 27-35
• 30 Wagner H R, Reches A, Yablonskaya E, Fahn S. Clonazepam-induced up-regulation of serotonin1 and serotonin2 binding sites in rat frontal cortex.  Adv. Neurol.. 1986;  43 645-651