Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD.

Repetitive transcranial magnetic stimulation (rTMS) has gained growing interest for the treatment of major depression (MDD) and treatment-resistant depression (TRD). Most knowledge on rTMS comes from human studies as preclinical application has been problematic. However, recent optimization of rTMS in animal models has laid the foundations for improved translational studies. Preclinical studies have the potential to help identify optimal stimulation protocols and shed light on new neurobiological-based rationales for rTMS use. To assess existing evidence regarding rTMS effects on depressive-like symptoms in rodent models, we conducted a comprehensive literature search in accordance with PRISMA guidelines (PROSPERO registration number: CRD42019157549). In addition, we conducted a meta-analysis to determine rTMS efficacy, performing subgroup analyses to examine the impact of different experimental models and neuromodulation parameters. Assessment of the depressive-like phenotype was quite homogeneous whilst rTMS parameters among the 23 included studies varied considerably. Most studies used a stress-induced model. Overall, results show a largely beneficial effect of active rTMS compared to sham stimulation, as reflected in the statistically significant recovery of both helplessness (SDM 1.34 [1.02;1.66]) and anhedonic (SDM 1.87 [1.02;2.72]) profiles. Improvement of the depressive-like phenotype was obtained in all included models and independently of rTMS frequency. Nonetheless, these results have limited predictive value for TRD patients as only antidepressant-sensitive models were used. Extending rTMS studies to other MDD models, corresponding to distinct endophenotypes, and to TRD models is therefore crucial to test rTMS efficacy and to develop cost-effective protocols, with the potential of yielding faster clinical responses in MDD and TRD.