Table 2.

Summary of randomised trials.

Study	Target	Sample Size, Sex (Age, Years)	Follow up	Stimulation Parameters	Effect on Tics Severity/YGTSS or MRVRS	Effect on Comorbidity	Adverse Effects/Comments
Maciunas et al. 2007 [39]	CMPf, Voi	Five males (18–34)	3	Variable polarity 3.5–3.6 V, 90–210 µs,130–180 Hz	Double blind comparison during first 4 weeks showed a 17% improvement. At 3 months 44% (mean) Non-responders with 4.3%–260% tic exacerbation	Mean score improvements: YBOCS 44%, BDI-2 60%, Hamilton anxiety scale, (HAS) 51%	One patient experienced acute psychosis during randomised period which was successfully treated. Overall three responders and two non-responders
Houeto et al. 2005 [62], Welter et al. 2008 [63]	CMPF and anteromedial GPi	Two females, one male (36, 30, 30)	60, 27, 20	CMPf: double monopolar 1.5–1.7 V, 60 µs, 130 Hz, Gpi: Single or double monopolar 1.5–3.5 V, 60 µs, 130 Hz	YGTSS cross-over period, (a)-AmGPi: (65%, 96%, 74%, (b)-CMPf: 30%, 40%, 64%, (c)-Gpi and CMPF 43%, 60%, 76% (after 60 months)	One patient previously had major depressive disorder and self-injurious behaviours and impulsiveness. Depressive mood, anxiety and impulsiveness tended to decrease with thalamic and pallidal stimulation but not paillidal sitmulation alone. None of the patients had OCD.	Reduced libido in one patient having thalamic stimulation. Lethargy, anxiety reported under pallidal stimulation and vertigo under higher intensity stimulation; arm paraesthesia under thalamic. Pallidal better than thalamic stimulation and both better than sham stimulation.
Ackermans et al. 2011 [40]	CM-Spv-Voi	6 males (completed full trial) (35–48 years)	36	1.3–7 V, 60–210 µs, 70–130 Hz. Monopolar stimulation in three patients and bipolar stimulation in the other three patients.	YGTSS at blinded ON compared to OFF stimulation was significantly lower (37%). After one year 49% and MRVRS 35%.	No significant difference found between the behavioural disorders and mood in the ON and OFF stimulation conditions.	One small haemorrhage ventral to electrode, one infection of pulse generator, subjective gaze disturbances which resolved after 6 months; all patient reported reduced energy levels. All patients when further questioned had subtle changes in oculomotor function, from visual disturbance to blurred vision and fixation problems, with no objective abnormalities detected with investigations. One younger patient with very severe SIB and life-threatening tics developed hypertonia, mutism and repeated fainting which needed extensive diagnostic evaluation- she was not randomised and considered loss to follow up. Only two patients completed the full 3 months on and of stimulation periods.
Kefalopoulou et al. 2015 [64]	AmGPi (13 patients), pvGPi (2 patients due to dystonic features).	11 males 4 females (25–55 years), 14 randomly assigned 13 completed assessments in both blinded periods. All 15 received stimulation in open-label phase	20–60	In blinded phase, 9 patients had monopolar and double monopolar in 4	YGTSS from off to on stimulation during blinded crossover period was 15.3%. Increased to 40.1% in open label phase	YBOCS-modest non-significant improvements Significant improvement in BDI GTS-QOL 38.9%	2 patients experienced infection of hardware requiring removal of leads and pulse generator with antibiotic treatment who were re-implanted 22 months later. One patient experienced deterioration of tics and hypomanic behaviour during on-stimulation periods, requiring stimulation parameter alterations and benzodiazepine treatment. 23 non-serious adverse events occurred, 15 of which resolved. During blinded phase, 6 patients had no clear benefit (<10% improvement in YGTSS) but most of these had more significant improvement in open label phase when parameters could be optimized. In open-label phase, 4 patients had less than 20% improvement n YGTSS.