Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders
Abstract
:1. Introduction
2. Literature Review
3. Major Depressive Disorder (MDD)
3.1. MDD and Lesional Procedures
3.1.1. Anterior Capsulotomy
3.1.2. Subcaudate Tractotomy
3.1.3. Anterior Cingulotomy
3.1.4. Limbic Leucotomy
3.2. MDD and MRgFUS
3.3. MDD and Radiosurgical Lesions
3.4. MDD and DBS
4. Obsessive-Compulsive Disorder (OCD)
4.1. OCD and DBS
4.2. Gamma-Knife and Radiofrequency Ablation for OCD
4.3. OCD and MRgFUS
5. Schizophrenia
Schizophrenia and Instrumental Therapeutics
6. Tourette’s Syndrome
DBS in Tourette’s Syndrome
7. Eating Disorders
7.1. Anorexia Nervosa and DBS
7.2. General Consideration about Eating Disorders
8. Addictions
9. Summary and Future Perspectives
10. Conclusions
11. Key Questions
- Have the right targets for each disease been individuated? Is neuroimaging sufficient to address this point?
- Is a single target sufficient to control all of the symptoms, given the emerging concept of altered connectivity between different structures?
- How can the connectomic approach help us in refining and improving surgical approach?
- Will aDBS improve results and be more effective in these patients?
- How can we solve the problem of non-responders? Is it possible to predict lack of efficacy and to find a biological hallmark for non-responsiveness for each disease?
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Technique | Step 1 | Step 2 | Step 3 | Treatment |
---|---|---|---|---|
GK | Positioning of a stereotactic frame to the patient’s head (for the target’s coordinates) | Acquisition of stereotactic MRI images for localizing the target; setup of the target’s coordinates | The patient and the sterotactic frame are fixed into a hemispherical helmet connected to the Main unit of the GK apparatus | The radiation sources are up to 201 γ radiation-emittingCobalt units connected to 4 or 8 mm collimators; the target is drawn on MRI images, and the total radiation dosage and radiation duration are decided for appropriate target lesioning (usually, single 4-mm isocenter with a maximum dose of 140–160 Gy |
RF | Positioning of a stereotactic frame to the patient’s head (for the target’s coordinates) | Acquisition of stereotactic MRI images for localizing the target; setup of the target’s coordinates | The patient is led to the operating room; target’s coordinates are brought into the sterile stereotactic apparatus | Two burr holes are made 3 cm in front of the coronal suture and 2.5 cm lateral to the midline; the thermoelectrode is inserted to the target and a thermic lesion is made |
DBS | Positioning of a stereotactic frame to the patient’s head (for the target’s coordinates) | Acquisition of stereotactic MRI images for localizing the target; setup of the target’s coordinates | The patient is led to the operating room; target’s coordinates are brought into the sterile stereotactic apparatus | Two burr holes are made 3 cm in front of the coronal suture and 2.5 cm lateral to the midline; the stimulating electrode is brought to the target structure and then fixed to the skull and connected to a subcutaneous internal pulse generator |
MRgFUS | Positioning of a stereotactic frame to the patient’s head (for the target’s coordinates) | Acquisition of stereotactic MRI images for localizing the target; setup of the target’s coordinates | The patient and the frame are fixed to the MRI FUS suite, which contains up to 1096 Ultrasound beams’ sources | The target is drawn on stereotactic MRI images; multiple and gradual sessions of US administration are performed, to reach lesional temperatures (at least 53 °C) with a variable amount of energy requirement (20.000–40.000 J) |
Technique | Author (Year) | Target | Patients | Study | Results |
---|---|---|---|---|---|
GK | Park (2016) | SI | 1 | OLS | HAMD17 decreased from 23 to 4 at 4 years FU |
RF | Christmas (2011) | ALIC | 20 | OLS | 50% response and 40% remission after 7 years’ FU |
RF | Hodgkis (1995) | SI | 183 | OLS | After one year-FU: 63 pts remitted, 53 had improved, 57 not changed or deteriorated |
RF | Ballantine (1967) | ACC | 26 | OLS | FU from 3 months to 4 years 20 pts: significantly improved; of these, 8 considered “well”; 6 pts: unsatisfactory results |
RF | Spangler (1996) | ACC | 15 | OLS | 60% of pts had a decrease in BDI of >50%; 12% of pts were “partial responders” |
RF | Shields (2008) | ACC | 33 | OLS | Mean FU of 30 months: 30% responders (>50% decrease in BDI); 40% partial responders (>35% decrease in BDI) or a CGI score ≤ 2 |
RF | Cho (2008) | ACC/SI | 16 | OLS | 68.8% of pts had a marked response (CGPSS ≥ 3); 18.9% had a possible response (CGPSS 2), 12.6% did not improve or worsened (CGPSS 0 or 1) |
RF | Montoya (2002) | ACC/SI | 6 | OLS | 3 out of six pts were responders according to physician-rated-assessment |
MRgFUS | Kim (2018) | ALIC | 1 | OLS | At one year, HDRS decreased from 26 to 7 and BDI from 26 to 12 |
DBS | Lozano (2012) | SCG | 21 | OLS | 50% reduction in HRSD: 57% of pts at 1 month, 48% at 6 months, 29%at 12 months |
DBS | Holtzheimer (2017) | SCG | 90 | RCT | No significant difference in response during the double-blind, sham-controlled phase |
DBS | Riva-Posse (2018) | SCG | 11 | OLS | 9 pts (81.8%) responders (HDRS decrease ≥ 50%) and 6 pts remitters (HDRS ≤ 7) at 12 months |
DBS | Schlaepfer (2008) | NAc | 3 | OLS | Mean HDRS dropped from 33.7 to 19.7 and mean MADRS mean 35.7 to 24.7 after one week FU |
DBS | Bewernick (2010) | NAc | 10 | OLS | 5 pts (50%) were responders (HDRS decrease ≥ 50%) at one-year FU |
DBS | Bewernick (2012) | NAc | 11 | OLS | 5 pts (45%) were responders at 2–4 years’ FU |
DBS | Malone (2009) | VC/VS | 15 | OLS | MADRS response rate was 53% and remission rate was 40% at one-year FU |
DBS | Dougherty (2015) | VC/VS | 30 | RCT | No significant difference in response rates between the active (20%) and the control (14.3%) groups; response rate at 2 years’ FU in Open-label phase was 23.3% |
DBS | Schlaepfer (2013) | MFB | 7 | OLS | 6 out of 7 pts responders (MADRS reduction ≥ 50%) and 4 out of 7 pts remitters (MADRS < 10) (FU 12–33 weeks) |
DBS | Fenoy (2016) | MFB | 4 | OLS | 3 out of 4 patients responders (MADRS score reduction ≥ 50%) at the last follow-up |
DBS | Bewernick (2017) | MFB | 8 | OLS | 6 out of 8 pts (75%) responders (MADRS score reduction ≥ 50%) and 4 pts (50%) remitters (MADRS < 10) at 12 months |
DBS | Sartorius (2010) | lHB | 1 | OLS | HDRS decreased from 35 to 0 after 12 weeks of high voltage DBS (10.5 V) and after relapse due to malfunction from bicycle accident |
DBS | Jimenez (2013) | ITP | 1 | OLS | HRDS decreased from 42 to 6 after 9-year FU |
Technique | Author (year) | Target | Study | Patients | Results |
---|---|---|---|---|---|
DBS | Nuttin (1999) | ALIC | OLS | 4 | 3 patients improvement and one of these had a 90% reduction in compulsive and ritual behaviours |
DBS | Jiménez (2007) | ITP | OLS | 1 | Decrease in Y-BOCS score from 40 to 15 at 15-month follow-up (37.5%) |
DBS | Huff (2010) | NAc | Double-blind controlled | 10 | Mean Y-BOCS scores decreased significantly from 32.2 to 25.4 at 1 year follow-up |
DBS | Franzini (2010) | NAc | OLS | 2 | Y-BOCS score improvement in both (Patient 1 from 38 to 22, Patient 2 from 30 to 20) |
DBS | Franzini (2015) | BNST (4); NAc (4) | OLS | 8 | 6/8 showed significant improvement at Y-BOCS |
DBS | Anderson (2003) | ALIC | OLS | 1 | 3-month postoperative Y-BOCS score was 7 (preoperatively 34) |
DBS | Sturm (2003) | NAc | OLS | 4 | Nearly total recovery in 3/4 |
DBS | Mallet (2008) | STN | Double-blind crossover | 16 | Y-BOCS score significantly lower than the score after sham stimulation (19.8 vs. 28) |
DBS | Abelson (2005) | ALIC | Pilot double-blind | 4 | Y-BOCS declined more with stimulators ON (19.8%) than with them OFF (10.5%) |
DBS | Greenberg (2010) | VC/VS | OLS | 26 | Mean Y-BOCS score decreased with stimulation, reaching 20.9 at 36 months (from 34 at baseline) |
DBS | Chabardes (2020) | STN | OLS | 19 | At 24-month follow-up, the mean Y-BOCS score improved by 53.4% (from 33.3 to 15.8) |
GK | Sheehan (2013) | ALIC | OLS | 5 | The mean Y-BOCS score improved from 32 to 13 |
GK (9), RF (16) | Rück (2008) | ALIC | OLS | 25 | The mean Y-BOCS score was 34 preoperatively and 18 at long-term follow-up |
GK | Rasmussen (2018) | ALIC | OLS | 55 | 31/55 (56%) improvement of ≥35% over the 3-year follow-up period at Y-BOCS |
MRgFUS | Kim (2018) | ALIC | OLS | 11 | The mean Y-BOCS score improved from 34.4 to 21.3 at 24-month follow-up |
MRgFUS | Davidson (2020) | ALIC | OLS | 7 | Response rate was 66.6% (>35% improvement in Y-BOCS score) |
Procedure | Author (Year) | Study Design | Targets | Sample Size | Outcomes | Comments |
---|---|---|---|---|---|---|
DBS | Plewnia (2008) | OLS | Right NAc | 1 | Reduction in symptoms (25% at Y-BOCS) and improvement in psychosocial functioning (58% at Global Assessment of Functioning) | Woman with intractable OCD and residual symptoms of schizophrenia |
DBS | Corripio (2020) | Randomized trial | NAc (n = 3); ACC (n = 4) | 7 | 2/3 of NAc and 2/4 of ACC reached a significant improvement in symptoms (≥25% increase at the PANSS total score) | 3/4 of responsive cases worsened after the pulse generator was switched; NAc exhibited a more marked and rapid improvement |
DBS | Wang (2020) | OLS | HB | 2 | Efficacy during the first 6 months, although only one patient maintained the result after one year | Positive symptoms were particularly improved |
Procedure | Author (Year) | Study Design | Targets | Sample Size | Outcomes | Comments |
---|---|---|---|---|---|---|
Lesional surgery | Baker (1962) | OLS | Bimedial frontal leucotomy | 1 | Marked reduction in tics and panic attacks at one-year follow-up | Postoperative complication of frontal abscess, successfully treated with evacuation and antibiotics |
Stereotactic lesioning | Hassler (1970) | OLS | Intralaminar, medial, and Voi nuclei of the thalamus | 3 | Significant tics’ reduction or resolution (100% in Patient 1, 90% in Patient 2, and 70% in Patient 3) | No details about the tic-rating method |
DBS | Vanderwalle (1999) | OLS | Intralaminar, medial, and Voi nuclei of the thalamus | 1 | At 1-year follow-up, tics resolved with stimulation | They decided to stimulate the thalamic nuclei targeted by Hassler |
DBS | Ackermans. (2011) | Double-blind randomized | Vo-CM-Pf | 6 | 49% improvement at a one-year follow-up at the YGTSS | Tic severity during ON stimulation was significantly lower than during OFF stimulation |
DBS | Servello (2016) | Cohort study | Vo-CM-Pf (n = 40); pGPi; aGPi; NAc-ALIC | 48 | Reduction in tics at the YGTSS of over 50% (78.4% in 29/37 cases examined) | Target 2 mm more anteriorly, reaching the associative-limbic connections |
DBS | Kefalopoulou (2015) | Double-blind randomized cross-over trial | aGPi (n = 13); pGPi (n = 2) | 15 | Total score at YGTSS significantly lower than in the off-stimulation phase (mean improvement of 12.4 points, 15.3%) | pGPi is part of the CSTC motor loop, while aGPi is part of the associative-limbic CSTC loop |
DBS | Kuhn (2007) | OLS | NAc/ALIC | 1 | Improvement in tics frequency and severity over two and half year follow-up (41% at YGTSS) | Also improvement of comorbid OCD |
DBS | Martinez-Torres et al. (2009) | OLS | STN | 1 | Tics frequency diminished by 97% at 1 year. In OFF stimulation immediate increase in tic frequency. | Comorbid PD: 57% improvement in the motor part of the Unified Parkinson’s Disease Rating Scale at 1 year |
DBS | Piedimonte (2013) | OLS | GPe | 1 | 70.5% improvement at YGTSS at six months | Loss of therapeutic effect with the battery exhausted |
GK | Richieri (2018) | OLS | ALIC | 1 | Clinical remission at 1 year | A case of intractable TS and OCD, non-responsive to DBS of pGPi and thalamus |
Eating Disorder | Procedure | Author (Year) | Study Design | Targets | Patients | Outcomes | Comments |
---|---|---|---|---|---|---|---|
AN | DBS | Wu (2013) | OLS | NAc | 4 | Average weight increase of 65% | Comorbid OCD in 3/4. Menstruation cycle restored in all patients in an average of 6.8 months |
AN | DBS | Lipsman (2013) | OLS | SCG | 6 | After 9 months, 3/6 increased BMI | Improvement in quality of life in three patients after 6 months |
AN | DBS | Lipsman (2017) | OLS | SCG | 16 | Mean BMI increased from 13.83 to 17.34 at 1 year | Significant improvements in depression and anxiety |
AN | DBS | Villalba Martínez (2020) | Double-blind randomized controlled crossover trial | SCG; NAc | 8 | After 6 months, 5/8 showed an increase of ≥10% in BMI | Target (SCG or NAc) selected according to comorbidities (affective or anxiety disorders) |
Pathological obesity | DBS | Harat (2016) | OLS | NAc | 1 | After 3 months, BMI decreased from 52.9 to 46.2 | Patient with hypothalamic obesity after craniopharyngioma surgery |
Author | Addiction | Outcome | Adverse Effects |
---|---|---|---|
Kuhn (2007) | Alcohol | Reduction of consumption from 10 (or more) drinks per day to 0–2 drinks per day | - |
Muller (2009) Voges (2013) Muller (2016) | Alcohol | All patients experienced loss of cravings; 2/5 pts maintained abstinence for 6–8 years; 2/5 pts maintained abstinence for 15–20 months followed by relapses; 1/5 pt reduced consumption with multiple short relapses | Hypomanic episode; migration of electrodes |
Kuhn (2009) | Nicotine | 3/10 patients stopped smoking at first attempt after surgery, maintaining cessation at 2-years FU | |
Gonçalves-Ferreira (2016) | Cocaine | Reduced use at 6 months and 24 months post-surgery; reduced severity of dependence at 2.5 years FU | Diminished libido; weight gain |
Zhou (2011) | Heroin | Mantained abstinence 6-years FU | Weight gain |
Valencia-Alfonso (2012) | Heroin | Mantained abstinence at 6-months FU | - |
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Vetrano, I.G.; Bonomo, G.; Messina, G. Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders. Psychiatry Int. 2021, 2, 1-24. https://doi.org/10.3390/psychiatryint2010001
Vetrano IG, Bonomo G, Messina G. Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders. Psychiatry International. 2021; 2(1):1-24. https://doi.org/10.3390/psychiatryint2010001
Chicago/Turabian StyleVetrano, Ignazio Gaspare, Giulio Bonomo, and Giuseppe Messina. 2021. "Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders" Psychiatry International 2, no. 1: 1-24. https://doi.org/10.3390/psychiatryint2010001