Author: Soriano-Mas, Carles ; Colzi, Carlotta ; Sauvaget, Anne ; Dell'Osso, Bernardo Maria ; Batail, Jean-Marie ; Pallanti, Stefano ; Szekely, David ; Pampaloni, Ilenia ; Van Ameringen, Michael ; Stein, Dan J ; Hollander, Eric ; Fontenelle, Leonardo F ; Nicolini, Humberto ; Drapier, Dominique ; Fusar-Poli, Paolo ; Brunoni, André R ; Arango, Celso ; Baeken, Chris ; Mayer-Linderberg, Andreas ; Voon, Valerie ; Rodriguez, Carolyn I ; Denys, Damian ; Lefaucheur, Jean-Pascal ; Vieta, Eduard ; Haffen, Emmanuel

Major depressive disorder (MDD) represents a major global health challenge, with a significant proportion of patients being resistant to drug treatment (TRD). Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the treatment of MDD/TRD, with a single stimulation session per day for five days per week over several weeks (the "standard" protocol). The two main paradigms used are high-frequency rTMS and intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (DLPFC). Accelerated TMS (aTMS) protocols aim to make the treatment more effective, or at least more rapidly effective, by delivering more stimulations in a shorter time, which could also facilitate the implementation of the protocols for a larger number of patients. In this systematic literature review, articles comparing in the same study an aTMS protocol to a standard or sham rTMS protocol were retained for analysis. Thus, 23 articles were retained and the analysis focused on the efficacy of aTMS protocols used for the treatment of depression (MDD/TRD) as well as on the impact of various stimulation parameters, such as stimulation pattern, intersession interval, dosage, and methods of cortical targeting. Although some studies did not report significant differences between aTMS and standard or sham protocols, others suggested potential advantages of aTMS, such as twice-daily HF-rTMS of the left DLPFC or more intensive iTBS protocols with a long interval between two sessions and personalized cortical targeting. Our results highlight the influence of the number of sessions or pulses per session (dosage), the duration of the interval between sessions, and the precision of target localization (using image-guided neuronavigation) on therapeutic efficacy. However, limitations in sample size, few independent studies replicating the same methodology, and variability in the clinical profile of treated patients, given different definitions of treatment resistance or the presence of comorbidities, hamper definitive conclusions.

01 Jan 2003·Schizophrenia Research

Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study

Article

Author: Nicolini, Humberto ; Kapur, Shitij ; Fresan, Ana ; Ulloa, Elena ; Apiquian, Rogelio ; Loyzaga, Cristina

OBJECTIVEAmoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of amoxapine in acutely psychotic patients with schizophrenia.METHODSSeventeen patients were enrolled and 15 completed a prospective open-label 6-week study of amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments.RESULTSAmoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p<0.001), with a trend towards improvement in mood symptoms and no treatment-emergent extrapyramidal side-effects, akathisia or weight gain. Prolactin elevation was observed.CONCLUSIONThese clinical data lend support to the pre-clinical suggestions that amoxapine may be an atypical antipsychotic. Given its lack of weight gain and that it is considerably less expensive than current options, amoxapine could be a valuable alternative for some patients. These considerations strongly call for more systematic, double-blind studies of amoxapine as an atypical antipsychotic.

Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder

Author: Rosário, Maria C ; Martin, Nicholas G ; Sampaio, Aline S ; Smit, Jan ; Soler, Artigas María ; Janecka, Magdalena ; Mors, Ole ; Nicolini, Humberto ; Mataix-Cols, David ; Zhou, Hang ; Stein, Murray B ; Falkai, Peter ; Hultman, Christina ; Wagner, Michael ; Reichenberg, Abraham ; Piacentini, John ; Veenstra-VanderWeele, Jeremy ; O'Connell, Kevin S ; Milani, Lili ; Cappi, Carolina ; Krasnow, Janice E ; Mathes, Brittany ; Bigdeli, Tim ; Buxbaum, Joseph D ; Burton, Christie L ; Børte, Sigrid ; Skogholt, Anne Heidi ; McLaughlin, Nicole C ; Kelley, Kara ; Grünblatt, Edna ; Andreassen, Ole A ; De Schipper, Elles J ; Black, Donald ; Gelernter, Joel ; Palviainen, Teemu ; Verweij, Karin J ; Richter, Margaret A ; Haavik, Jan ; Grove, Jakob ; Rodriguez-Fontenla, Cristina ; Strom, Nora I ; Kathmann, Norbert ; Boberg, Julia ; Ciullo, Valentina ; Hougaard, David M ; Kaprio, Jaakko ; Walker, Christopher P ; Storch, Eric A ; Bloch, Michael H ; Fyer, Abby J ; Sandor, Paul ; Turiel, Maurizio ; Meier, Sandra ; Bucholz, Kathleen K ; Rabionet, Raquel ; Garner, Lauryn ; Ripke, Stephan ; Krebs, Kristi ; Lanzagorta, Nuria ; Mattheisen, Manuel ; Le Hellard, Stéphanie ; Fernandez, Thomas V ; Luykx, Jurjen J ; Karlsson, Elinor K ; Wang, Ying ; Sloofman, Laura G Sloofman G ; Nissen, Judith Becker ; Stranger, Barbara E ; Rasmussen, Steven A ; Banaj, Nerisa ; Schiele, Miriam A ; Kvale, Gerd ; Elias, Jason A ; Gironda, Christina ; Zai, Gwyneth ; Djurovic, Srdjan ; Hanna, Gregory L ; Cullen, Bernadette A ; Bosch, Rosa ; Reichborn-Kjennerud, Ted ; Crosby, Jesse ; Bybjerg-Grauholm, Jonas ; Brentani, Helena ; Pauls, David L ; Nurmi, Erika L ; Landén, Mikael ; Scharf, Jeremiah M ; Neale, Benjamin M ; Lai, Dongbing ; Ramirez, Alfredo ; van Kirk, Nathanial ; Carracedo, Angel ; Mahjani, Behrang ; Rosenberg, David R ; Bulik, Cynthia M ; Goes, Fernando S ; Harrington, Kelly ; Alemany, Silvia ; Domschke, Katharina ; Zwart, John-Anker ; Estivill, Xavier ; Casas, Miguel ; Coleman, Jonathan R ; Tifft, Eric ; Mathews, Carol A ; Medland, Sarah E ; Winsvold, Bendik S ; Maher, Brion ; Leboyer, Marion ; Grados, Marco A ; Derks, Eske M ; Pedersen, Nancy L ; Arnold, Paul D ; Børglum, Anders D ; Jenike, Eric ; Galimberti, Marco ; Crowley, James J ; Pato, Carlos ; Berberich, Götz ; Mortensen, Preben B ; Delorme, Richard ; Cath, Danielle ; Cook, Edwin H ; Ask, Helga ; Yu, Dongmei ; Macciardi, Fabio ; Barlassina, Cristina ; Agrawal, Arpana ; Greenberg, Benjamin D ; Samuels, Jack F ; Hveem, Kristian ; Yao, Yin ; Byrne, Enda M ; German, Chris ; Brennan, Brian P ; Halvorsen, Matthew W ; McCracken, James T ; Breen, Gerome ; Havdahl, Alexandra ; Piras, Fabrizio ; Abdellaoui, Abdel ; Rauch, Scott ; Piras, Federica ; Kennedy, James ; Grice, Dorothy E ; Sealock, Julia M ; Grabe, Hans J ; Wendland, Jens R ; Lange, Christoph ; Breen, Michael ; McGregor, Nathaniel ; Hickie, Ian B ; Stewart, S Evelyn ; Smit, Dirk J ; Nestadt, Paul S ; Stein, Dan J ; Fundin, Bengt T ; Cavallini, Maria Cristina ; Levey, Daniel ; Pato, Michele ; Falkenstein, Martha J ; Riddle, Mark A ; Sandin, Sven ; Geller, Dan A ; Camarena, Beatriz ; Mulhern, Maureen ; Andre, Christine ; Hucks, Donald ; Thorp, Jackson G ; Hansen, Bjarne K ; McArthur, Evonne ; Posthuma, Danielle ; Ribasés, Marta ; Gaziano, J M ; Camarena, Adrian ; Höffler, Kira D ; Alonso, Pino ; Vallada, Homero ; Bey, Katharina ; Askland, Kathleen D ; Miguel, Euripedes C ; Guo, Wei ; Ruhrmann, Stephan ; Ousdal, Olga Therese ; Hounie, Ana G ; Walitza, Susanne ; Cabana-Dominguez, Judit ; Lochner, Christine ; Knowles, James A ; Ramos-Quiroga, Josep Antoni ; Klawohn, Julia ; Hagen, Kristen ; Spalletta, Gianfranco ; Vulink, Nienke N ; Bienvenu, O Joseph ; Pittenger, Christopher ; Rück, Christian P ; Eapen, Valsamma ; Osiecki, Lisa ; Werge, Thomas ; Thomas, Laurent F ; Nordentoft, Merete ; Edenberg, Howard ; Nestadt, Gerald ; Potluri, Sriramya ; Gerring, Zachary F ; Davis, Lea K ; Denys, Damiaan ; Lindblad-Toh, Kerstin

AbstractObsessive-compulsive disorder (OCD) affects ∼1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, includingWDR6, DALRD3, CTNND1and multiple genes in the MHC region. We estimated that ∼11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and cortex, along with D1- and D2-type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all of the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa, and Tourette syndrome, and was negatively associated with inflammatory bowel diseases, educational attainment, and body mass index.

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