Table 2.
Summary of the results of controlled studies of promising pharmacological agents
| Study | Primary/social outcome | Treatment effect | Placebo effect | Effect size/sig | Secondary outcomes |
|---|---|---|---|---|---|
| Risperidone | |||||
| Scahill et al. [127] | |||||
| Study 1 [128] | ABC-SW (2) | 0.42 | ABC | ||
| Study 2 [129] | ABC-SW (2) | 0.65 | ABC | ||
| Naharaj et al. [130] | CARS/CGAS (1) | Sig | GIR | ||
| Social responsiveness item of parent questionnaire (2) | Sig | ||||
| Arbaclofen | |||||
| Delahunty et al. [139] | ABC-SW (1) | NS | ABC, CGI-I, CGI-S, VABS | ||
| Bumetanide | |||||
| Lemonnier et al. [140] | CARS (1) | − 5.6 ± 4.0 | − 1.8 ± 5.1 | CGI-TI, ADOS | |
| ADOS: reciprocity (2) | NS | ||||
| Lemonnier et al. [141] | CARS (1) | 0.5 mg: − 5.0 ± 4.3 1.0 mg: − 3.1 ± 3.3 2.0 mg: − 3.2 ± 4.0 |
− 1.6 ± 2.3 | SRS, CGI-I | |
| SRS (2) | 0.5 mg: − 12.4 ± 23.6 1.0 mg: − 13.2 ± 20.5 2.0 mg: − 21.8 ± 19.8 |
− 1.6 ± 20.4 | |||
| Memantine | |||||
| Ghaleiha et al. [148] | ABC-SW (2) | NS | ABC | ||
| Aman et al. [107] | SRS (1) | NS | CATS, CAASTS, CCC-2, CGI, ABC | ||
| Propanolol | |||||
| Zamzow et al. [151] | GSOM (1) | 0.40 | SCAS, BAI, ECG, SC | ||
| Zamzow et al. [152] | Facial scanning | ||||
| Mouth (1) | 0.59 | HR, BP | |||
| Eyes/nose (1) | NS | ||||
| Oxytocin (single) | |||||
| Hollander et al. [159] | Affective speech Comprehension (1) | 0.66 | None | ||
| Guastella et al. [160] | RMET (1) | 49 ± 15% | 45 ± 18% | ||
| Auyeung et al. [161] | Facial scanning (no. of fixations) | ||||
| Eyes (1) | 0.86 | Total fixation time | |||
| Mouth/other (1) | NS | Subgroup analysis | |||
| Kanat et al. [162] | House–face dot-probe Paradigm (100 ms/500 ms) | Correlation with social anxiety | |||
| Reaction time (1) | NS | ||||
| Attentional bias (1) | NS | ||||
| Adherence (1) | NS | ||||
| Allocation (500 ms) (1) | Sig | ||||
| Oxytocin (prolonged) | |||||
| Anagnostou et al. [163] | RBS-R (1) | 0.64 | RMET, SRS, YBOCS, WHOQOL–E | ||
| DANVA/CGI (1) | NS | ||||
| Watanabe et al. [165] | ADOS (1) | ||||
| Reciprocity | − 8.8 ± 15.2 | 12.2 ± 24.1 | 0.78 | rsFC, AQ, SRS, RBS-R, STAI, CESD, QOL, CGI-E, GAF | |
| Communication/repetitive | NS | ||||
| CARS (1) | NS | ||||
| Yatawara et al. [166] | SRS (1) | 13.5 ± 17.2 | 5.2 ± 17.3 | ADOS, DBC, CGI-I, CSQ | |
| RBS-R (1) | NS | ||||
| Dadds et al. [113] | Family interaction task (1) | NS | Global ratings of social interaction, SSRS, SRS-AM, OACIS, CARS, FERT, DISCAP-ASD | ||
| Guastella et al. [167] | SRS/CGI-I (1) | NS | DBC, RBS-R, RMET, DANVA, Biological motion | ||
| Kosaka et al. [168] | CGI-I overall (1) | NS | ABC, ZSRDS, STAI, TAS | ||
| ABC-SW (2) | NS | ||||
| Vasopressin | |||||
| Umbricht et al. [185] | Biological motion | ABC, ASR, CGI-I, RMET, STAI, SCIT, OI | |||
| Orienting preference | 0.80 | ||||
| Composite | NS | ||||
| Bolognani et al. [186] | SRS | NS | VABS, ABC, RBS-R, CGI-I, STAI, ADAMS | ||
| Leucovorin calcium | |||||
| Frye et al. [82] | Verbal communication (1) | 0.70 | VABS, ABC, OACIS, ASQ, SRS, AIM | ||
| ABC-SW (2) | Sig | ||||
| SRS (2) | NS | ||||
| Cobalamin | |||||
| Hendren et al. [194] | CGI-I (1) | 0.70 | ABC, SRS | ||
| ABC-SW (2) | NS | ||||
| SRS social motivation (2) | 0.73 | ||||
| SRS other (2) | NS | ||||
| N -acetyl- l -cysteine | |||||
| Hardan et al. [196] | ABC-I (1) | 0.96 | ABC, RBS-R, SRS, CGI-I | ||
| ABC-SW (2) | NS | ||||
| SRS social cognition (2) | 0.99 | ||||
| SRS other (2) | NS | ||||
| Ghanizadeh et al. [197] | ABC-I (1) | 0.14 | ABC | ||
| ABC-SW (2) | NS | ||||
| Nikoo et al. [198] | ABC-I (1) | 9.3 ± 4.1 | 5.4 ± 3.2 | ABC | |
| ABC-SW (2) | NS | ||||
| Dean et al. [199] | SRS, CCC-2, RBS-R (1) | NS | DBC-P, PGI-I, CGI-I, CGI-S | ||
| Wink et al. [200] | CGI-I (1) | NS | CGI-S, ABC, SRS, VABS | ||
| ABC-SW/SRS (2) | NS | ||||
| Tetrahydrobiopterin | |||||
| Danfors et al. [201] | CARS: overall | NS | CARS: communication and stereotyped behavior | ||
| CARS: social interactions | 1.6 ± 1.1 | 0.3 ± 1.4 | |||
| Klaiman et al. [202] | CGI-I/CGI-S | NS | PLS, SRS, ABC, VABS | ||
| SRS social awareness | Sig | ||||
| SRS autism mannerism | Sig | ||||
| ABC-SW | NS | ||||
| Carnitine | |||||
| Geier et al. [203] | CARS | 1.9 ± 2.5 | 0.1 ± 1.4 | ||
| CGI | − 0.5 ± 0.6 | 0.1 ± 0.7 | |||
| ATEC total | NS | ||||
| ATEC sociability | NS | ||||
| Hand strength | NS | ||||
| Fahmy et al. [204] | CARS | Sig | |||
| Sulforaphane | |||||
| Singh et al. [205] | ABC total | 21.4 ± 4.5 | 2.0 ± 3.5 | None | |
| SRS total | 20.4 ± 4.5 | 2.0 ± 3.5 | |||
| OACIS: improved | |||||
| Social | 46% | 0% | |||
| Aberrant behavior | 54% | 9% | |||
| Verbal | 42% | 0% | |||
| Other scales | NS | ||||
The primary outcome for all studies is given. If the primary outcome is not a measure of social function, then secondary outcomes that reflect social function are listed. The number in parenthesis after the outcome measures indicates whether it is a primary or secondary outcome measure. Studies that did not have any social outcome measures were not included in this table
ABC Aberrant Behavior Checklist, ABC-I ABC-Irritability Subscale, ABC-SW ABC-Social Withdrawal Subscale, ADAMS Anxiety, Depression and Mood Scale, ADOS Autism Diagnostic Observation Schedule, AIM Autism Impact Measure, AQ Autism Spectrum Quotient, ASR affective speech recognition, ASQ Autism Symptoms Questionnaire, ATEC Autism Treatment Evaluation Checklist, BAI Beck Anxiety Inventory, BP blood pressure, CAASTS Core and Associated Autism Symptom Treatment Scale, CARS Childhood Autism Rating Scale, CATS Core Autism Treatment Scale, CATS-I Core Autism Treatment Scale-Improvement, CCC-2 Children’s Communication Checklist-2, CESD Centre for Epidemiologic Studies Depression Scale, CGAS Children’s Global Assessment Scale, CGI Clinical Global Impression Scale, CGI-E CGI-Efficacy, CGI-I CGI-Improvement, CGI-S CGI-Severity Scale, CGI-TI CGI-Therapeutic Index, CSQ Caregiver Strain Questionnaire, DANVA Diagnostic Analysis of Nonverbal Accuracy, DBC Developmental Behavior Checklist, DBC-P Developmental Behavioural Checklist-Primary Caregiver Version, DISCAP-ASD Diagnostic Interview Schedule for Children, Adolescents, and Parents, ECG electrocardiography, FERT facial emotion recognition task, GAF Global Assessment of Functioning, GIR General Improvement Rating, GSOM Conversational Reciprocity task of the General Social Outcome Measure, HR heart rate, NS no significant differences between treatment and placebo group, PGI-I Parent Global Impression-Improvement, PLS Preschool Language Scales, QOL quality-of-life questionnaire, OACIS Ohio Autism Clinical Impression Scale, OI olfactory identification, RBS-R Repetitive Behaviour Scale-Revised, RMET Reading Mind in the Eyes Test, rsFC resting-state functional connectivity, SC skin conductance, SCAS Spence Children’s Anxiety Scale, SCIT Scripted Communication and Interaction Test, Sig significant differences between treatment and placebo group, SRS Social Responsiveness Scale, SRS-AM Social Reciprocity Scale Autistic Mannerisms, SSRS Social Skills Rating Scale, STAI State and Trait Anxiety Inventory, TAS Toronto Alexithymia Scale, VABS Vineland Adaptive Behavior Scale, WHOQOL-E World Health Organization Quality of Life Questionnaire - emotional/social subscales, YBOCS Yale Brown Obsessive Compulsive Scale, ZSRDS Zung Self-Rating Depression Scale