Current Neuropharmacology - Volume 17, Issue 8, 2019

Background: The lifespan approach and recent shift in the conceptualization of Obsessive- Compulsive Disorder (OCD) promoted by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM5) along with novel insights into the pathogenesis of this heterogeneous disorder are driving the development of new outcome measures and new treatments for a disease that, on the other hand, is characterized by high rates of refractoriness. Objective and Methods: The aim of this review is to provide a discussion of the translational evidence about Early Onset OCD (EO) in compliance with a neurodevelopmental and RdoC perspective. Results and Conclusion: EO might be considered the neurodevelopmental subtype of OCD. Indeed there is evidence that different clusters of symptoms and dimensions at an early stage predict different trajectories in phenotype and that distinct neurocircuit pathways underpin the progression of the disorder. Despite the development of high refractoriness in the course of the disorder, evidence suggests that EO may be particularly treatment responsive in the early stages, thus showing the need for early recognition and additional recovery oriented studies in this subgroup. Consistent with the neurodevelopmental perspective, immunity and glutamate neurotransmission are emerging as novel pathways for parsing out the neurobiology of OCD, the EO form, in particular, supporting the implementation of new multisystemic models of the OCD phenotype. Brain connectivity patterns, immune and microbiome profiles are standing out as promising areas for biomarkers with the potential for targeted personalized therapies in EO.

Background: Historically, OCD has been considered to be associated with a relatively low risk of suicide. Recent studies, on the contrary, revealed a significant association between OCD and suicide attempts and ideation. A huge variation in prevalence rates, however, is reported. Objective: To estimate prevalence rates of suicide attempts and suicidal ideation in individuals with OCD, and to identify predictors of suicide risk among subjects with OCD. Methods: We systematically reviewed the literature on suicide risk (ideation and/or attempts) and OCD. We included studies with appropriate definition of OCD, cross-sectional or prospective design, separating clinical samples from epidemiological studies, that employed a quantitative measure of suicidality and/or reported an outcome measure of the association between suicidality and OCD or examined factors associated with suicidality. Results: In clinical samples, the mean rate of lifetime suicide attempts is 14.2% (31 studies: range 6- 51.7%). Suicidal ideation is referred by 26.3-73.5% of individuals (17 studies, mean 44.1%); current suicidal ideation rate ranges between 6.4 and 75% (13 studies, mean 25.9). Epidemiological studies found that OCD increases significantly the odds of having a lifetime suicidal ideation as compared to the general population (OR: 1.9-10.3) and a history of lifetime suicide attempts (OR: 1.6- 9.9). Predictors of greater suicide risk are severity of OCD, the symptom dimension of unacceptable thoughts, comorbid Axis I disorders, severity of comorbid depressive and anxiety symptoms, past history of suicidality and some emotion-cognitive factors such as alexithymia and hopelessness. Conclusion: Overall, suicidality appears a relevant phenomenon in OCD.

Body dysmorphic disorder is a challenging disorder that manifests as erroneously perceived flaws in one’s physical appearance and repetitive behaviors in response to appearance concerns. This disorder is also frequently comorbid with other psychiatric disorders, including major depressive disorder and autism spectrum disorder. It is currently understood to arise from a combination of biological, psychological, and environmental factors. Treatment of body dysmorphic disorder typically consists of a combination of pharmacotherapy and cognitive behavioral therapy. However, not all patients respond to treatment, and BDD symptoms remain even in those who do respond. This review outlines current pharmacological and neuromodulation treatments for body dysmorphic disorder and suggests directions for future studies of novel treatments such as augmentation with atypical antipsychotics and the use of intranasal oxytocin in cases of body dysmorphic disorder that show residual symptomatology even with tailored monotherapy. There is emerging evidence suggesting that non-invasive neurostimulatory techniques, such as repetitive transcranial magnetic stimulation, may be of value in treatment-resistant cases.

While Behavioral Therapy (BT) should be recommended as the first step in the treatment of OCD as well as TS, medication can be added for augmentation and in certain situations (e.g. family preference, BT not available or feasible) the priority may even reverse. This narrative review is given on the complexity of drug treatment in patients comorbid with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) and other tic problems. OCD with TS is a co-occurring combination of the two generally delimitable, but in detail, also overlapping disorders which wax and wane with time but have different courses as well as necessities and options of treatment. Distinct subtypes like “tic-related OCD” are questionable. Obsessive-compulsive symptoms (OCS) and tics are frequently associated (OCS in TS up to 90%, tics in OCD up to 37%). Sensory-motor phenomena like urges and just-right feelings reflect some behavioral overlap. The main additional psychopathologies are attention-deficit hyperactivity disorder (ADHD), mood problems and anxiety. Also, hair pulling disorder and skin picking disorder are related to OCD with TS. Hence, the assessment and drug treatment of its many psychopathological problems need high clinical experience, careful planning, and ongoing evaluation/adaptation. Drugs are able to reduce clinical symptoms but cannot cure the disorders, which should be treated in parallel in their own right; i.e. for OCD serotonin reuptake inhibitors (SSRI) and for TS (tics), certain antipsychotics can be successfully prescribed. In cases of OCD with tics, when OCS responds only partially, an augmentation with antipsychotics (recommended: risperidone and aripiprazole) may improve OCS as well as tics. Also, the benzamide sulpiride, an atypical antipsychotics, may be beneficial in treating the combination of OCS, tics and anxious-depressive problems. Probably, any additional psychopathologies of OCD might attenuate the effectiveness of SSRI on OCS; on the other hand, in cases of OCD with tics, SSRI may reduce not only OCS but also stress sensitivity and emotional problems and thus leading to better selfregulatory abilities, useful to improve tic suppression. In sum, some clinical guidance can be given, but there remain many uncertainties because of a scarce database for psychopharmacotherapy in OCD with TS.

Background: Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have considerable societal costs due to healthcare service utilization. Objective: Our aim was to assess the efficacy of pharmacological interventions in OCD and clinical guidelines, providing a comprehensive overview of this field. Methods: We searched the PubMed database for papers dealing with drug treatment of OCD, with a specific focus on clinical guidelines, treatments with antidepressants, antipsychotics, mood stabilizers, off-label medications, and pharmacogenomics. Results: Prolonged administration of selective serotonin reuptake inhibitors (SSRIs) is most effective. Better results can be obtained with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly oriented exposure and response prevention (ERP). Refractory OCD could be treated with different strategies, including a switch to another SSRI or clomipramine, or augmentation with an atypical antipsychotic. The addition of medications other than antipsychotics or intravenous antidepressant administration needs further investigation, as the evidence is inconsistent. Pharmacogenomics and personalization of therapy could reduce treatment resistance. Conclusions: SSRI/clomipramine in combination with CBT/ERP is associated with the optimal response compared to each treatment alone or to other treatments. New strategies for refractory OCD are needed. The role of pharmacogenomics could become preponderant in the coming years.

Obsessive-compulsive disorder (OCD) is an important disorder which is disturbing the quality of life and is characterized by repetitive thoughts and behaviors, now in a different category in the Diagnostic and Statistical Manual for Mental Disorders Fifth Edition (DSM 5). Neuroimaging investigations are very useful to reveal a neurobiological model of the OCD. Studies conducted in the last quarter century have shown clear results and revealed that specific cortico-subcortical circuits could be involved in the occurrence of OCD symptomatology. These neuroimaging studies pointed out some important findings for OCD patients. Our present information implicates some problems in some cortico-subcortical in the pathophysiology of OCD. In the present paper, final information on the neuroanatomy and neurochemistry of OCD was reviewed, revising the effects of anti-obsessional drugs on the structural and functional neuroimaging studies. As can be seen in the review, drug treatments can generally affect the brain structurally and functionally, suggesting that brain of OCD tends to neuroplasticity. However, it is not clear that these effects of pharmacotherapy are related to anti-obsessional drugs per se or impact on the improvement of the disorder.

Background: Placebo response appears to be increasing in antidepressant, antipsychotic and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999. Placebo response is generally considered as the extent to which placebo treatment is associated with core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend of both placebo response and placebo responder rates according to the year of publication with no time restriction in OCD drug trials. Methods: We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase, CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR OCD). We included studies through investigator consensus. We then performed on data of included studies log-linear joinpoint segmented regression models using a p<0.05 cutoff. Results: We included 113 studies from 112 published papers. Placebo mean annual response rates in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of 0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017, with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show statistically significant APC changes between 1984 and 2017. Conclusion: We observed a tendency for placebo to increase both measures of response in OCD clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes in the type of study (moving from classical head to head comparisons to add-on studies in treatmentresistant populations) and countries involved in experimentation may partially account for some portion of these results. It appears that placebo effects are becoming more elusive and out of control.

Background: Trichotillomania (TTM), excoriation (or skin-picking) disorder and some severe forms of onychophagia are classified under obsessive-compulsive and related disorders. There are different interacting neurotransmitter systems involved in the pathophysiology of impulse-control disorders, implicating noradrenaline, serotonin, dopamine, opioid peptides and glutamate, hence investigators focused on drugs able to act on these transmitters. Our aim was to critically review the efficacy of the drugs employed in impulse-control disorders. Methods: We searched for controlled drug trials to treat TTM, excoriation, and/or nail-biting six databases (PubMed, Cochrane, Scopus, CINAHL, PsycINFO/PsycARTICLES, and Web of Science), using the search strategy: (trichotillomania OR “excoriation disorder” OR “face picking” OR “skin picking” OR “hair pulling” OR onychophagia OR “nail-biting”) AND drug treatment on 12 March 2018 for all databases. We followed in our method of identifying relevant literature the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: SSRIs and clomipramine are considered first-line in TTM. In addition, family members of TTM patients are often affected by obsessive-compulsive spectrum disorders. Other drugs used in the treatment of TTM are lamotrigine, olanzapine, N-Acetylcysteine, inositol, and naltrexone. Conclusion: The treatment of TTM, excoriation disorder and nail-biting is still rather disappointing. Conjectures made from preclinical studies and the relative pathophysiological hypotheses found poor confirmations at a clinical level. There is a need for further studies and the integration of pharmacological and psychotherapeutic. Our results point to the need of integrating personalised medicine principles in the treatment of these patients.

Background: Obsessive-compulsive disorder (OCD) is a highly prevalent, severe, and chronic disease. There is a need for alternative strategies for treatment-resistant OCD. Objective: This review aims to assess the effect of brain stimulation techniques in OCD. Methods: We included papers published in peer-reviewed journals dealing with brain stimulation techniques in OCD. We conducted treatment-specific searches for OCD (Technique AND ((randomized OR randomised) AND control* AND trial) AND (magnetic AND stimulation OR (rTMS OR dTMS)) AND (obsess* OR compuls* OR OCD)) on six databases, i.e., PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials and ClinicalTrials.gov for possible additional results. Results: Different add-on stimulation techniques could be effective for severely ill OCD patients unresponsive to drugs and/or behavioural therapy. Most evidence regarded deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), while there is less evidence regarding transcranial direct current stimulation (tDCS), electroconvulsive therapy, and vagus nerve stimulation (for these last two there are no sham-controlled studies). Low-frequency TMS may be more effective over the supplementary motor area or the orbitofrontal cortex. DBS showed best results when targeting the crossroad between the nucleus accumbens and the ventral capsule or the subthalamic nucleus. Cathodal tDCS may be better than anodal in treating OCD. Limitations. We had to include methodologically inconsistent underpowered studies. Conclusion: Different brain stimulation techniques are promising as an add-on treatment of refractory OCD, although studies frequently reported inconsistent results. TMS, DBS, and tDCS could possibly find some use with adequate testing, but their standard methodology still needs to be established.

This brief review deals with the various issues that contributed to the creation of the new Diagnostic and Statistical Manual condition of hoarding disorder (HD) and attempts at reviewing its pharmacotherapy. It appears that after the newly founded diagnosis appeared in the literature as an autonomous entity, distinct from obsessive-compulsive disorder, drug trials are not being conducted and the disorder is left in the hands of psychotherapists, who on their part, report fair results in some core dimensions of HD. The few trials on HD specifically regard the serotonin-noradrenaline reuptake inhibitor venlafaxine, and, possibly due to the suggestion of a common biological background of HD with attention-deficit/hyperactivity disorder, the psychostimulant methylphenidate and the noradrenaline reuptake inhibitor atomoxetine. For all these drugs, positive results have been reported, but the evidence level of these studies is low, due to small samples and non-blind designs. Regretfully, there are currently no future studies aiming at seriously testing drugs in HD.