Deep brain stimulation of the internal capsule or the nucleus accumbens in patients with obsessive-compulsive disorder: where to modulate?
Objective: Several targets have been implicated in the study of the effects of deep brain stimula... more Objective: Several targets have been implicated in the study of the effects of deep brain stimulation (DBS) on obsessive-compulsive disorder (OCD) symptomatology. The most common targeted areas are the nucleus accumbens (Nacc), the internal capsule (IC), the ventral capsule/ventral striatum, and[for full text, please go to the a.m. URL]
ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for ... more ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofro...
Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the con... more Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus–nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of ...
C Co oy yu un nt tu ur ra a C ada vez que los calendarios electorales de los países latinoamerica... more C Co oy yu un nt tu ur ra a C ada vez que los calendarios electorales de los países latinoamericanos han coincidido, como en esta oportunidad (véase Tabla 1), los debates académicos y de políticos profesionales han interpretado a la coyuntura como un momento de disyunción. La versión en boga sostiene que América Latina, tras el largo predominio del neoliberalismo que caracterizó a los años ochenta y noventa, estaría finalmente dando un giro hacia la izquierda. 1 Alternativamente, desde el campo liberal se ha avanzado en la propuesta de que la coyuntura actual no hace más que continuar el proceso de liberalización de la política en la región, reforzando la interacción entre democracia y liberalización económica (Wise, 2003: 2). Estas hipótesis rivales padecen del defecto de ser lecturas ideológicas ex post de las conductas de los gobiernos recientemente electos, en proceso de renovación, o incluso de meras candidaturas presidenciales y mal definidos programas políticos. En los Andes, la puesta a prueba de estas hipótesis debe aguardar por lo menos una década más, aunque no sea sino por las fechas del calendario electoral pendiente y porque el futuro permanece incierto. El presente trabajo se aleja de las interpretaciones ideológicas, de izquierda y liberales, para examinar a la luz de la evidencia empírica la hipótesis de que la coyuntura actual sea, en efecto, crítica, pero que no marca el giro hacia la izquierda, sino la culminación de un largo período de ajuste político en los Andes. Entiendo por "ajuste político", un proce-a a o o e el le ec ct to or ra al l e en n l lo os s A An nd de es s E El l f fi in n d de el l a aj ju us st te e e ec co on n m mi ic co o? ?
Inflammation plays a key role in the development of sensitization after peripheral nerve damage. ... more Inflammation plays a key role in the development of sensitization after peripheral nerve damage. We recently demonstrated that tumor necrosis factor-a receptor (TNFR) levels in the spinal cord correlate with pain sensation in herniated disc patients in a rat chronic constriction injury (CCI) model. By using the sciatic nerve CCI model, we studied the effect of anti-TNF-a treatment on recovery from hypersensitivity and TNFR expression in the dorsal root ganglion (DRG) and dorsal horn (DH). Experimental groups consisted of shamoperated and CCI-operated rats that received two s.c. injections (one immediately after surgery, the other 5 days later), both containing saline, etanercept (3 mg/kg body weight), or infliximab (10 mg/kg body weight). Mechanical allodynia (with von Frey filaments) and thermal hyperalgesia (Hargreaves test) were assessed preoperatively and weekly during the first 4 postoperative weeks. DRG and DH samples were collected 2 and 4 weeks after surgery and analyzed for TNFR1 and TNFR2 protein levels by Western blotting and analyzed for mRNA levels by quantitative real-time polymerase chain reaction. Anti-TNF-a treatment resulted in a significant alleviation of pain. TNFR levels were increased five-to sixfold in CCI rats compared with sham controls. Both treatments significantly diminished these increased levels. Treated animals that showed a 50% alleviation of pain exhibited a significantly reduced TNF R1/R2 mRNA ratio compared with treated animals that recovered less well. These results demonstrate that attenuation of TNFR expression is associated with recovery from nerve injury and suggest that this may be one of the working mechanisms of anti-TNF therapies. V
Estimate the effects of methylprednisolone (MP) administration and olfactory bulb (OB) implantati... more Estimate the effects of methylprednisolone (MP) administration and olfactory bulb (OB) implantation independently and in combination after a spinal trauma model in Wistar rats, evaluated with BBB scale and CBS with remark of inclined plane test and Tarlov scale. Thirty adult rats were divided into six different groups, evaluated before trauma, one day post-surgery and weekly up to six weeks post-lesion. Group A (control); group B (sham) laminectomy without lesion; group C (SCI) lesion only; group D (MP) SCI and MP; group E (OB) SCI and OB implantation; group F (MP/OB) SCI and both therapeutics. Intragroup data at three weeks showed evident significance in groups D, E and F for Tarlov (p = 0.001) and BBB (p < 0.01); groups C, D, E and F for CBS (p < 0.05); and only group D with inclined plane (p < 0.05). On the sixth week differences were present in groups C, D, E, and F for Tarlov, BBB and CBS (p < 0.001); and C and F for inclined plane (p < 0.05). For intergroup analysis any treatment showed differences with Tarlov scale; for BBB and inclined plane, statistical differences were evident in groups E and F; and for CBS only in group F (p < 0.05). Real effects of MP are obtained at immediate follow-up, without notorious augmentation after time. OB improvement is achieved only after weeks. None of these therapies used independently achieve a constant and sustained improvement. Combined treatments were more effective and reached higher functional levels for longer periods of time.
Tumor necrosis factor-alpha (TNF-a) is a principal mediator in pro-inflammatory processes that in... more Tumor necrosis factor-alpha (TNF-a) is a principal mediator in pro-inflammatory processes that involve necrosis, apoptosis and proliferation. Experimental and clinical evidence demonstrate that peripheral nerve injury results in activation and morphological changes of microglial cells in the spinal cord. These adjustments occur in order to initiate an inflammatory cascade in response to the damage. Between the agents involved in this reaction, TNF-a is recognized as a key player in this process as it not only modulates lesion formation, but also because it is suggested to induce nociceptive signals. Nowadays, even though the function of TNF-a in inflammation and pain production seems to be generally accepted, diverse sources of literature point to different pathways and outcomes. In this review, we systematically searched and reviewed original articles from the past 10 years on animal models of peripheral nervous injury describing TNF-a expression in neural tissue and pain behavior.
Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with ga... more Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with gait and frequently accompanied by severe pain. The authors report the case of a 28-year-old woman with history of perinatal hypoxia, who presented with cerebral palsy and severe spastic diplegia (Ashworth Scale Score 4, Tardieu Scale Score 5) and was confined to a wheelchair. She complained of pain in the left hip and knee with mixed neuropathic and somatic components. She consistently rated pain intensity as 10 of 10 on a visual analog scale, and her symptoms were resistant to multiple treatments. The patient underwent selective bilateral adductor myotomies and the implantation of an infusion pump for intrathecal lidocaine application. Postoperative control of pain and spasticity was dramatic (scores of 0 on the Ashworth, Tardieu, and visual analog scales) and persisted throughout a follow-up period of 36 months. This is the first report in the literature of combined selective neurotomie...
Purpose Previous experimental models have shown that proinflammatory cytokines modulate periphera... more Purpose Previous experimental models have shown that proinflammatory cytokines modulate peripheral and central nociception. However, the direct correlation between inflammation and pain in patients remains unclear. Our aim is to correlate the levels of inflammation in the spine with pre-and postoperative pain scores after discectomy. Methods Paravertebral muscle, annulus fibrosus (AF) and nucleus pulposus (NP) biopsies were intraoperatively collected from ten lumbar disc hernia (LDH) patients suffering from chronic sciatic pain and, as painless controls, five scoliosis patients. IL-1b and IL-6 expressions in these biopsies were assessed by qPCR and western blot. The amount of pain, indicated on a 0-10 point visual analogue scale (VAS), was assessed 1 day before surgery and 6 weeks and 1 year after surgery. For analysis purposes, LDH patients were grouped into painful (VAS C 3.5) and non-painful (VAS \ 3.5). LDH painful patient group showed a onefold increased mRNA expression of IL-1b in the NP, and IL-6 in the AF and NP (p \ 0.05 vs. controls). Results By western blot analysis, both cytokines were clearly visible in all LDH biopsies, but not in controls. However, cytokine expression of the painful patient group did not differ from those of the non-painful patient group. In addition, there was no correlation between VAS scores and either marker. Conclusions These findings support the idea that LDH is accompanied by a local inflammatory process. Yet, the lack of correlation between IL-1b or IL-6 expression and the severity pain suggests that these cytokines may not play a leading role in maintaining a pain generating network.
The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is well recognized as a key player i... more The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is well recognized as a key player in nociceptive signaling. Yet, therapeutic capitalization of this knowledge requires a better understanding of how TNF receptors (TNFR) contribute to pain. To address this question, we studied TNFR expression in the chronic sciatic nerve constriction (CCI) model of neuropathic pain. CCI and sham operated rats received two subcutaneous injections (one immediately after surgery, the other on postoperative day 5) containing either saline, GABA-reuptake inhibitor (NO-711), insulin-like growth factor-1 (IGF-1), ZVAD or thalidomide. Mechanical (using von Frey filaments) and thermal hypersensitivity (Hargreaves test) were assessed preoperatively and weekly during the first four postoperative weeks. Spinal cord dorsal horn samples were collected from animals that were sacrificed at 2 weeks and 4 weeks after surgery, and analyzed for TNFR1 and TNFR2 mRNA levels by qPCR and protein levels by Western blot. Compared to saline, all applied drug treatments resulted in a faster recovery from mechanical and thermal hypersensitivity, yet in a potency order of thalidomide > ZVAD = IGF-1 > NO-711. CCI resulted in increased TNFR1 and TNFR2 mRNA and protein levels in the ipsilateral dorsal horn. Thalidomide was the only treatment that attenuated these increases. Finally, animals that showed a poor behavioral recovery were characterized by a significantly higher TNFR1/TNFR2 mRNA ratio. These data show that differential expression of TNFR in the dorsal horn is associated with recovery from pain in this model and suggest that the analgesic effects of thalidomide may act via this mechanism.
Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst ... more Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods.
Deep brain stimulation of the internal capsule or the nucleus accumbens in patients with obsessive-compulsive disorder: where to modulate?
Objective: Several targets have been implicated in the study of the effects of deep brain stimula... more Objective: Several targets have been implicated in the study of the effects of deep brain stimulation (DBS) on obsessive-compulsive disorder (OCD) symptomatology. The most common targeted areas are the nucleus accumbens (Nacc), the internal capsule (IC), the ventral capsule/ventral striatum, and[for full text, please go to the a.m. URL]
ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for ... more ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofro...
Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the con... more Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus–nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of ...
C Co oy yu un nt tu ur ra a C ada vez que los calendarios electorales de los países latinoamerica... more C Co oy yu un nt tu ur ra a C ada vez que los calendarios electorales de los países latinoamericanos han coincidido, como en esta oportunidad (véase Tabla 1), los debates académicos y de políticos profesionales han interpretado a la coyuntura como un momento de disyunción. La versión en boga sostiene que América Latina, tras el largo predominio del neoliberalismo que caracterizó a los años ochenta y noventa, estaría finalmente dando un giro hacia la izquierda. 1 Alternativamente, desde el campo liberal se ha avanzado en la propuesta de que la coyuntura actual no hace más que continuar el proceso de liberalización de la política en la región, reforzando la interacción entre democracia y liberalización económica (Wise, 2003: 2). Estas hipótesis rivales padecen del defecto de ser lecturas ideológicas ex post de las conductas de los gobiernos recientemente electos, en proceso de renovación, o incluso de meras candidaturas presidenciales y mal definidos programas políticos. En los Andes, la puesta a prueba de estas hipótesis debe aguardar por lo menos una década más, aunque no sea sino por las fechas del calendario electoral pendiente y porque el futuro permanece incierto. El presente trabajo se aleja de las interpretaciones ideológicas, de izquierda y liberales, para examinar a la luz de la evidencia empírica la hipótesis de que la coyuntura actual sea, en efecto, crítica, pero que no marca el giro hacia la izquierda, sino la culminación de un largo período de ajuste político en los Andes. Entiendo por "ajuste político", un proce-a a o o e el le ec ct to or ra al l e en n l lo os s A An nd de es s E El l f fi in n d de el l a aj ju us st te e e ec co on n m mi ic co o? ?
Inflammation plays a key role in the development of sensitization after peripheral nerve damage. ... more Inflammation plays a key role in the development of sensitization after peripheral nerve damage. We recently demonstrated that tumor necrosis factor-a receptor (TNFR) levels in the spinal cord correlate with pain sensation in herniated disc patients in a rat chronic constriction injury (CCI) model. By using the sciatic nerve CCI model, we studied the effect of anti-TNF-a treatment on recovery from hypersensitivity and TNFR expression in the dorsal root ganglion (DRG) and dorsal horn (DH). Experimental groups consisted of shamoperated and CCI-operated rats that received two s.c. injections (one immediately after surgery, the other 5 days later), both containing saline, etanercept (3 mg/kg body weight), or infliximab (10 mg/kg body weight). Mechanical allodynia (with von Frey filaments) and thermal hyperalgesia (Hargreaves test) were assessed preoperatively and weekly during the first 4 postoperative weeks. DRG and DH samples were collected 2 and 4 weeks after surgery and analyzed for TNFR1 and TNFR2 protein levels by Western blotting and analyzed for mRNA levels by quantitative real-time polymerase chain reaction. Anti-TNF-a treatment resulted in a significant alleviation of pain. TNFR levels were increased five-to sixfold in CCI rats compared with sham controls. Both treatments significantly diminished these increased levels. Treated animals that showed a 50% alleviation of pain exhibited a significantly reduced TNF R1/R2 mRNA ratio compared with treated animals that recovered less well. These results demonstrate that attenuation of TNFR expression is associated with recovery from nerve injury and suggest that this may be one of the working mechanisms of anti-TNF therapies. V
Estimate the effects of methylprednisolone (MP) administration and olfactory bulb (OB) implantati... more Estimate the effects of methylprednisolone (MP) administration and olfactory bulb (OB) implantation independently and in combination after a spinal trauma model in Wistar rats, evaluated with BBB scale and CBS with remark of inclined plane test and Tarlov scale. Thirty adult rats were divided into six different groups, evaluated before trauma, one day post-surgery and weekly up to six weeks post-lesion. Group A (control); group B (sham) laminectomy without lesion; group C (SCI) lesion only; group D (MP) SCI and MP; group E (OB) SCI and OB implantation; group F (MP/OB) SCI and both therapeutics. Intragroup data at three weeks showed evident significance in groups D, E and F for Tarlov (p = 0.001) and BBB (p < 0.01); groups C, D, E and F for CBS (p < 0.05); and only group D with inclined plane (p < 0.05). On the sixth week differences were present in groups C, D, E, and F for Tarlov, BBB and CBS (p < 0.001); and C and F for inclined plane (p < 0.05). For intergroup analysis any treatment showed differences with Tarlov scale; for BBB and inclined plane, statistical differences were evident in groups E and F; and for CBS only in group F (p < 0.05). Real effects of MP are obtained at immediate follow-up, without notorious augmentation after time. OB improvement is achieved only after weeks. None of these therapies used independently achieve a constant and sustained improvement. Combined treatments were more effective and reached higher functional levels for longer periods of time.
Tumor necrosis factor-alpha (TNF-a) is a principal mediator in pro-inflammatory processes that in... more Tumor necrosis factor-alpha (TNF-a) is a principal mediator in pro-inflammatory processes that involve necrosis, apoptosis and proliferation. Experimental and clinical evidence demonstrate that peripheral nerve injury results in activation and morphological changes of microglial cells in the spinal cord. These adjustments occur in order to initiate an inflammatory cascade in response to the damage. Between the agents involved in this reaction, TNF-a is recognized as a key player in this process as it not only modulates lesion formation, but also because it is suggested to induce nociceptive signals. Nowadays, even though the function of TNF-a in inflammation and pain production seems to be generally accepted, diverse sources of literature point to different pathways and outcomes. In this review, we systematically searched and reviewed original articles from the past 10 years on animal models of peripheral nervous injury describing TNF-a expression in neural tissue and pain behavior.
Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with ga... more Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with gait and frequently accompanied by severe pain. The authors report the case of a 28-year-old woman with history of perinatal hypoxia, who presented with cerebral palsy and severe spastic diplegia (Ashworth Scale Score 4, Tardieu Scale Score 5) and was confined to a wheelchair. She complained of pain in the left hip and knee with mixed neuropathic and somatic components. She consistently rated pain intensity as 10 of 10 on a visual analog scale, and her symptoms were resistant to multiple treatments. The patient underwent selective bilateral adductor myotomies and the implantation of an infusion pump for intrathecal lidocaine application. Postoperative control of pain and spasticity was dramatic (scores of 0 on the Ashworth, Tardieu, and visual analog scales) and persisted throughout a follow-up period of 36 months. This is the first report in the literature of combined selective neurotomie...
Purpose Previous experimental models have shown that proinflammatory cytokines modulate periphera... more Purpose Previous experimental models have shown that proinflammatory cytokines modulate peripheral and central nociception. However, the direct correlation between inflammation and pain in patients remains unclear. Our aim is to correlate the levels of inflammation in the spine with pre-and postoperative pain scores after discectomy. Methods Paravertebral muscle, annulus fibrosus (AF) and nucleus pulposus (NP) biopsies were intraoperatively collected from ten lumbar disc hernia (LDH) patients suffering from chronic sciatic pain and, as painless controls, five scoliosis patients. IL-1b and IL-6 expressions in these biopsies were assessed by qPCR and western blot. The amount of pain, indicated on a 0-10 point visual analogue scale (VAS), was assessed 1 day before surgery and 6 weeks and 1 year after surgery. For analysis purposes, LDH patients were grouped into painful (VAS C 3.5) and non-painful (VAS \ 3.5). LDH painful patient group showed a onefold increased mRNA expression of IL-1b in the NP, and IL-6 in the AF and NP (p \ 0.05 vs. controls). Results By western blot analysis, both cytokines were clearly visible in all LDH biopsies, but not in controls. However, cytokine expression of the painful patient group did not differ from those of the non-painful patient group. In addition, there was no correlation between VAS scores and either marker. Conclusions These findings support the idea that LDH is accompanied by a local inflammatory process. Yet, the lack of correlation between IL-1b or IL-6 expression and the severity pain suggests that these cytokines may not play a leading role in maintaining a pain generating network.
The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is well recognized as a key player i... more The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is well recognized as a key player in nociceptive signaling. Yet, therapeutic capitalization of this knowledge requires a better understanding of how TNF receptors (TNFR) contribute to pain. To address this question, we studied TNFR expression in the chronic sciatic nerve constriction (CCI) model of neuropathic pain. CCI and sham operated rats received two subcutaneous injections (one immediately after surgery, the other on postoperative day 5) containing either saline, GABA-reuptake inhibitor (NO-711), insulin-like growth factor-1 (IGF-1), ZVAD or thalidomide. Mechanical (using von Frey filaments) and thermal hypersensitivity (Hargreaves test) were assessed preoperatively and weekly during the first four postoperative weeks. Spinal cord dorsal horn samples were collected from animals that were sacrificed at 2 weeks and 4 weeks after surgery, and analyzed for TNFR1 and TNFR2 mRNA levels by qPCR and protein levels by Western blot. Compared to saline, all applied drug treatments resulted in a faster recovery from mechanical and thermal hypersensitivity, yet in a potency order of thalidomide > ZVAD = IGF-1 > NO-711. CCI resulted in increased TNFR1 and TNFR2 mRNA and protein levels in the ipsilateral dorsal horn. Thalidomide was the only treatment that attenuated these increases. Finally, animals that showed a poor behavioral recovery were characterized by a significantly higher TNFR1/TNFR2 mRNA ratio. These data show that differential expression of TNFR in the dorsal horn is associated with recovery from pain in this model and suggest that the analgesic effects of thalidomide may act via this mechanism.
Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst ... more Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods.
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