Table 2.
Intranasal oxytocin treatment trials in patients with schizophrenia stable on antipsychotic drugs: effects on positive symptoms, negative symptoms and cognitive deficits2. Adapted from [58].
| Author | N | Dosing/Duration | Results:Positive Symptoms | Negative Symptoms | Cognitive Deficits |
|---|---|---|---|---|---|
| Acute Studies | All study designs | ||||
| Averbeck et al. 2011 [72] | Exp 1: 30 SCZ (24 M, 6 F), 29 CTL, Exp 2: 21 SCZ M | 24 IU, single dose | NA | NA | OT treatment improved ability of patients to recognize most emotions (hexagon emotion discrimination test) |
| Goldman et al. 2011 [73] | 13 SCZ, 5 PS (3 M, 2 F), 8 NPS (4 M, 4 F) 11 CTL |
10 or 20 IU, single dose | NA | NA | 10 IU dose caused decreased emotion recognition due to emotion overidentification. 20 IU dose improved emotion recognition PS vs. NPS, specifically around fear recognition |
| Fischer-Shofty et al. 2013a [74] | 35 SCZ (31 M, 4 F), 48 CTL | 24 IU, single dose crossover design | NA | NA | OT improved recognition of kinship (Interpersonal Perception Task) |
| Fischer-Shofty et al. 2013b [112] | 30 SCZ (27 M, 3 F) 35 CTL |
24 IU, single dose crossover design | NA | NA | OT facilitated recognition of fearful facial expression in patients and controls |
| Davis et al. 2013 [75] | 23 SCZ, OT 11 M, PL 12 M |
40 IU, single dose | NA | NA | OT improved perception of sarcasm, deception and empathy (EPTT, Eckman Facial Recognition Task) |
| Horta de Macedo, et al., 2014[113] | 20 SCZ M 20 CTL |
48 IU, single dose | NA | NA | Facial affect processing not improved by OT |
| Woolley et al. 2014 [76] | 29 SCZ M 31 CTL |
40 IU, single dose | NA | NA | OT improved controlled (ability to comprehend indirect expression of emotion, thoughts and intentions) but not automatic (emotional cues in voices, faces and body language) social cognition in SCZ |
| Michalopoulou et al. 2015 [64] | 21 SCZ OT 11 M PL 10 M |
20 IU single dose, | NA | NA | OT improved the “executive component” of working memory (Digispan) |
| Shin et al. 2015 [79] | 16 SCZ M 16 CTL |
40 IU, single dose cross over design | NA | NA | OT decreased amygdala activity for fearful faces and increased activity (fMRI) for happy faces (Emotion recognition test) |
| Guastella 2015 [77] | 24 SCZ M | 24 IU, single dose, cross over design | NA | NA | OT improved higher-order social cognition such as appreciation of indirect hints and recognition of social faux pas |
| Clinical Trials | |||||
| Feifel et al. 2010 [62] | 15 SCZ 12 M, 3 F |
40 IU twice daily 3 weeks/crossover design |
OT improved PANSS positive subscale and CGI after 3 weeks | OT improved negative subscale after 3 weeks | See [63] |
| Pederson et al. 2011 [65] | 20 SCZ OT 9 M, 2 F PL 8 M, 1 F |
24 IU twice daily 2 weeks |
OT improved PANSS positive subscale after 2 weeks | OT improved PANSS negative subscale | Improvement in identification of second false beliefs and trends toward significant improvement in accurate recognition of deception and rating untrustworthy faces as untrustworthy (Brune task) |
| Feifel et al. 2012 [63] | See Feifel et al. 2010 [62] | 40 IU twice daily 3 weeks/crossover design |
NA | NA | OT improved verbal learning (CVLT) but not working memory (LNS) after 3 weeks |
| Modabbernia et al. 2013 [66] | 40 SCZ 20 OT 17 M, 3 F 20 PL 8 M, 1 F |
40 IU twice daily 8 weeks |
OT improved PANSS positive subscale starting at 8 weeks | OT improved PANSS negative subscale after eight weeks | NA |
| Lee et al. 2013 [67] | 28 SCZ OT 9 M, 4F PL 8 M, 7 F Included schizo-affective |
20 IU twice daily 3 weeks |
Positive symptoms (BPRS) not improved vs. PL after 3 weeks | Negative symptoms (BPRS) improved in small group of inpatients patients after 3 weeks | NA |
| Gibson et al. 2014 [68] | 14 SCZ OT 6 M, 2 F PL 5M, 1 F |
24 IU twice daily 6 weeks |
Both OT and PL groups exhibited significant improvement in PANSS positive subscale after 6 weeks | OT improved PANSS negative subscale after six weeks | OT but not PL decreased fear recognition and perspective taking component of empathy after 6 weeks (ER-40) |
| Cacciotti-Saija et al. 2014 [70] | 52 SCZ SCT + OT M 18, F 9 SCT + PL 18 M, 7 F |
40 IU twice daily 6 weeks |
OT did not improve positive symptoms (SAPS) beyond SCT when given in combination with 6 weeks of SCT | Increased use of IN OT, but not PL was correlated with lower SANS scores | Six weeks of daily OT added to SCT did not enhance the SCT greater than PL |
| Davis et al. 2014 [71] | 27 SCZ SCT + OT M 13 SCT + PL M 14 |
40 IU twice weekly 6 weeks |
OT did not improve positive symptoms (BPRS) beyond SCT when given in combination with 6 weeks of SCT | Six weeks of OT added to SCT did not improve negative symptoms (CAINS) | Six weeks of OT added to SCT enhanced social cognitive benefits (empathic accuracy) greater than PL, lasting at least one month |
Abbreviations: BPRS, Brief Psychiatric Research Survey; CAINS, Clinical Assessment Interview for Negative Symptoms; CTL, controls; CVLT, California Verbal Learning Test; EPTT, emotional perspective taking task; ER-40, The Emotion Recognition 40; LNS, Letter Number Sequence; NPS, non poydipsic; PANSS, Positive and Negative Symptom survey; PL, placebo; PS, polydipsic; SANS, Scale for Assessment of Negative symptoms; SAPS, Scale for Assessment of Positive Symptoms; SCT, social cognitive test; SCZ, schizophrenia
Several decades ago, investigators in the USSR published two letters [114, 115] describing open-label experience using OT to treat patients with “SCZ” and a small randomized study [116] of OT in “SCZ” subjects. These reports suggested that OT had therapeutic effects. However, these reports contain clinical descriptions and terminology that do not correspond to contemporary concepts of SCZ. Furthermore, the rigor of methodology and reporting is well below accepted current standards. These shortcomings significantly limit the value of these early reports to shed light on the effects of OT in SCZ