rTMS of the Dorsomedial Prefrontal Cortex for Major Depression:Safety,Tolerability,Effectiveness,and Outcome Predictors for 10Hz Versus Intermittent Theta-burst Stimulation
Nathan Bakker a ,c ,1,Saba Shahab a ,d ,1,Peter Giacobbe a ,b ,Daniel M.Blumberger b ,c ,e ,Za ?ris J.Daskalakis b ,c ,e ,Sidney H.Kennedy b ,c ,Jonathan Downar a ,b ,c ,e ,*
a
MRI-Guided rTMS Clinic,Department of Psychiatry,University Health Network,399Bathurst Street,Room 7M-415,Toronto,Ontario,Canada M5T 2S8b
Department of Psychiatry,University of Toronto,250College Street,Floor 8,Toronto,Ontario,Canada M5T 1R8c
Institute of Medical Science,University of Toronto,Faculty of Medicine,Medical Sciences Building,1King ’s College Circle,Room 2374,Toronto,Ontario,Canada M5S 1A8d
Faculty of Arts and Sciences,University of Toronto,100St.George Street,Toronto,Ontario,Canada M5S 3G3e
Temerty Centre for Therapeutic Brain Intervention at the Centre for Addiction and Mental Health,Toronto,Ontario,Canada
a r t i c l e i n f o
Article history:
Received 26August 2014Received in revised form 2November 2014
Accepted 3November 2014
Available online 22November 2014Keywords:rTMS
Theta burst stimulation Dorsomedial Depression Bipolar Predictor Case series Chart review
a b s t r a c t
Background:Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30min.However,recent studies have sought to improve costs,capacities,and outcomes by employing briefer protocols such as theta burst stimulation (iTBS).
Objective:To compare safety,effectiveness,and outcome predictors for DMPFC-rTMS with 10Hz (30min)versus iTBS (6min)protocols,in a large,naturalistic,retrospective case series.
Methods:A chart review identi ?ed 185patients with a medication-resistant major depressive episode who underwent 20-30sessions of DMPFC-rTMS (10Hz,n ?98;iTBS,n ?87)at a single Canadian clinic from 2011to 2014.
Results:Clinical characteristics of 10Hz and iTBS patients did not differ prior to treatment,aside from signi ?cantly higher age in iTBS patients.A total 7912runs of DMPFC-rTMS (10Hz,4274;iTBS,3638)were administered,without any seizures or other serious adverse events,and no signi ?cant differences in rates of premature discontinuation between groups.Dichotomous outcomes did not differ signi ?cantly between groups (Response/remission rates:Beck Depression Inventory-II:10Hz,40.6%/29.2%;iTBS,43.0%/31.0%.17-item Hamilton Rating Scale for Depression:10Hz,50.6%/38.5%;iTBS,48.5%/27.9%).On continuous outcomes,there was no signi ?cant difference between groups in pre-treatment or post-treatment scores,or percent improvement on either measure.Mixed-effects modeling revealed no sig-ni ?cant group-by-time interaction on either measure.
Conclusions:Both 10Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120%resting motor threshold.The effectiveness of 6min iTBS and 30min 10Hz protocols appears comparable.Randomized trials comparing 10Hz to iTBS may be warranted.
ó2015The Authors.Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND
license (https://www.doczj.com/doc/c715360333.html,/licenses/by-nc-nd/3.0/).
Introduction
Repetitive transcranial magnetic stimulation (rTMS)is an emerging treatment for medication-resistant major depressive disorder (MDD),which affects approximately 2%of the population [1].The most recent studies of rTMS in MDD have achieved fairly consistent response rates of 50e 55%and remission rates of 30e 35%in naturalistic case series and open-label trials [2e 4].However,although the ?rst human studies of rTMS in MDD took place nearly 25years ago [5,6],the optimal parameters of stimulation are still under investigation.
Abbreviations:rTMS,repetitive transcranial magnetic stimulation;MDD,major depressive disorder;TRD,treatment-resistant depression;DLPFC,dorsolateral prefrontal cortex;DMPFC,dorsomedial prefrontal cortex;iTBS,intermittent theta burst stimulation;HamD17,17-item Hamilton Depression Rating Scale;BDI-II,Beck Depression Inventory-II;MINI,Mini International Neuropsychiatric Interview;DSM,Diagnostic and Statistical Manual;FDR,false discovery rate.
The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation,the Buchan Family Foundation,and the Ontario Brain Institute in funding this work.
*Corresponding author.MRI-Guided rTMS Clinic,Department of Psychiatry,University Health Network,399Bathurst Street 7M-415,Toronto,Ontario,Canada M5T 2S8.Tel.:t14166035667.
E-mail address:jonathan.downar@uhn.ca (J.Downar).1
Authors NB and SS made equal contributions to this
work.
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Brain Stimulation
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https://www.doczj.com/doc/c715360333.html,/10.1016/j.brs.2014.11.002
1935-861X/ó2015The Authors.Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license (https://www.doczj.com/doc/c715360333.html,/licenses/by-nc-nd/3.0/).
Brain Stimulation 8(2015)208e 215
One key parameter is the stimulation target.The most widely used target for rTMS in MDD is the dorsolateral prefrontal cortex (DLPFC).However,convergent evidence from lesion,stimulation, neuroimaging,and connectivity studies also implicates a variety of other prefrontal regions in MDD[7,8].Of these,the DMPFC has received the most attention to date.Recent case reports in MDD[9], case series in MDD and bipolar disorder[10,11],and studies in post-traumatic stress disorder[12]and eating disorders[13]have pro-vided initial proof-of-concept evidence that DMPFC-rTMS may be safe,tolerable,and effective in MDD and other mood and anxiety disorders.However,as of this writing,it remains unclear whether DMPFC-rTMS matches or exceeds the effectiveness of conventional DLPFC stimulation overall,or indeed whether different sub-populations of MDD patients might respond preferentially to DMPFC-versus DLPFC-rTMS.
Another key parameter for optimization is the stimulation pro-tocol itself.The most widely used protocol[14,15]applies3000 pulses of10Hz stimulation to the left DLPFC over37.5min.How-ever,lengthy protocols limit the number of patients who can be treated per day per device,which in turn obliges a high cost-per-session($250e350in many areas).A protocol with the same effectiveness but shorter duration(5e10min)could permit up to ?ve-fold increases in treatment capacity,which in turn would permit lower treatment charges.Such improvements would greatly facilitate wider affordability and adoption of rTMS as a mainstream treatment for MDD,as has been seen with other outpatient medical procedures(such as laser vision correction)where technical im-provements allowed higher case volumes and lower per-procedure charges.
A promising form of patterned rTMS is theta-burst stimulation (TBS),which applies50Hz triplet bursts?ve times per second[16]. Intermittent theta burst stimulation(iTBS),on a2s on/8s off cycle, delivers600pulses in just over3min.This pattern has been found to have an excitatory effect whose potency matches or exceeds much longer sessions of conventional rTMS[17].If brief iTBS ses-sions could be shown to have equivalent antidepressant effective-ness to longer10Hz sessions,the translational implications for rTMS capacity and affordability would be tremendous.
To date,at least2case series have used some form of TBS in MDD,and each has demonstrated that TBS is safe,tolerable,and at least comparably effective to conventional stimulation[18,19]. More recently,2randomized controlled trials have demonstrated superior antidepressant ef?cacy of TBS over sham rTMS[20,21]. However,as of this writing,there has been no explicit comparison of the ef?cacy of iTBS versus conventional10Hz stimulation in MDD.
The de?nitive demonstration of non-inferiority for iTBS over 10Hz rTMS will require a substantially larger patient sample and a randomized controlled design.However,in the interim,evidence from large-N,open-label case series may help to inform the design of future studies.As an example,several large open-label series have helped to establish the optimal course length for DLPFC-rTMS in the average range26e28sessions[2,22].
We have previously reported outcomes,and neuroimaging correlates of outcome,for two small case series of patients under-going10Hz DMPFC-rTMS for a major depressive episode[10,11]. Here,we report data from a chart review of a larger series of185 patients who received20e30sessions of open-label,add-on rTMS of the left and right DMPFC,delivered as either10Hz stimulation or iTBS,for treatment of a major depressive episode,over a3-year period at a single high-volume clinic.Data from patients receiving DLPFC-rTMS will be reviewed in a subsequent work,due to an insuf?cient number of DLPFC cases available for analysis at present.
We hypothesized a priori based on previous observations[17]1) that both10Hz and iTBS of the DMPFC would be safe,tolerable,and effective;2)that iTBS would not differ signi?cantly from10Hz DMPFC-rTMS in terms of effectiveness on self-reported or clinician-rated measures.In addition,based on previous observations[11], we hypothesized3)that outcomes for DMPFC-rTMS would show a non-normal,bimodal distribution for both10Hz and iTBS;4)that pre-treatment anhedonia symptoms would predict response to DMPFC-rTMS using either iTBS or10Hz stimulation.
Materials and methods
Chart review and patient population
This chart review encompassed data on stimulation parameters, tolerability,safety,and effectiveness on self-and clinician-rated symptom scales for every patient who received open-label,add-on rTMS of the bilateral DMPFC at the University Health Network’s MRI-Guided rTMS Clinic between April2011and February2014for treatment of a major depressive episode,whether in the context or unipolar or bipolar illness.Throughout this period,this clinic accepted community referrals and offered treatment without charge to every referred patient free of pre-speci?ed clinical con-traindications to rTMS(active substance use disorders;psychotic disorders;neurological disorders;rTMS or MRI contraindications, including implanted devices,foreign ferromagnetic metal bodies, uncontrolled cardiac arrhythmias,unstable medical conditions,a history of epileptic seizures,traumatic brain injury or other central neurological abnormality,or pregnancy).The de?ned period for this retrospective case series ended with the onset of substantial recruitment volumes to a subsequent prospective randomized controlled trial,currently in progress.
Following referral,all patients completed the Mini International Neuropsychiatric Interview(MINI)6.0screen,and then underwent a full clinical psychiatric assessment(including multi-axial diag-nosis)by a Canadian Royal College-certi?ed psychiatrist(JD or PG) using DSM-IV criteria.Responses to the MINI screen were used to identify diagnostic categories for additional scrutiny during inter-view.All patients had a history of resistance to at least two adequate medication trials(including discontinuations due to adverse effects),and at least one trial in the current episode,based on clinical interview supplemented by medical and pharmacy re-cords.To maximize the generalizability of the reported results to real-world practice,no co-morbidities were used as exclusion criteria in this chart review.Likewise,in order to better re?ect clinical practice,treatment was offered to all patients with illness severe enough that they were willing to attend a course of at least 20sessions of rTMS;thus,no a priori minimum threshold of symptom severity was applied.As a standard clinical practice,all patients were required to maintain a consistent regimen of medi-cations for4weeks prior to treatment,and throughout the treat-ment course,to help disambiguate the source of any symptomatic improvement or decline.All patients provided informed consent for rTMS prior to initiating treatment,following UHN guidelines for clinical procedure consent.This chart review was approved by the Research Ethics Board of the University Health Network.
DMPFC-rTMS procedures
The neuronavigation,motor threshold,and coil placement pro-cedures for DMPFC-rTMS,as practiced here,have been previously described in detail elsewhere[10,13].rTMS was delivered using a MagPro R30device equipped with a Cool D-B80Coil(MagVenture, Farum,Denmark)and a Qooler high-performance cooling system, under MRI guidance using the Visor2.0system(Advanced Neuro Technologies,Enschede,Netherlands)in all cases.Stimulation tar-geted the left then right DMPFC at120%of the resting motor
N.Bakker et al./Brain Stimulation8(2015)208e215209
threshold for extensor hallucis longus.All patients initially received 20sessions of treatment;those who achieved response but not remission criteria were offered an additional10sessions.rTMS was administered one session per day,5days per week,for a total of4e6 weeks.Missed sessions were added to the end of the treatment course to achieve the target number of sessions per course;no patient missed more than4cumulative sessions per course.
Each session of10Hz stimulation applied3000pulses to the left hemisphere then again to the right hemisphere(6000pulses total), with a duty cycle of5s on and10s off,for a total stimulation time w30min.Each session of iTBS applied600pulses per hemisphere (1200pulses total),for a total stimulation time w6min.As these treatments were provided in a clinical context rather than a research trial,patients were not randomly allocated.Instead,since both treatments were permissible under Health Canada regula-tions,treatment selection followed an informed consent discussion with the patient,incorporating factors such as the extent of the evidence base for safety and ef?cacy,tolerability,and wait time to begin treatment(wait times for iTBS were shorter due to the briefer appointments required),as well as the availability of more con-ventional alternatives to DMPFC-rTMS at public and private clinics in the same downtown Toronto area.For consistency,a single investigator(JD)conducted all such discussions.
Clinical assessments
A standard clinical practice was instituted for monitoring progress in all patients undergoing rTMS for major depression. Patients received baseline clinical assessments one week before treatment,interim clinical assessments after each?ve sessions of treatment,and follow-up clinical assessments2,4,6,and12weeks after treatment.Clinical assessments included the17-item Hamil-ton Rating Scale for Depression-17(HamD17)[23]and the Beck Depression Inventory-II(BDI-II)[24].Response was de?ned as !50%symptom reduction from pre-to post-treatment;remission criteria were set at a post-treatment score7for HamD17,12for BDI-II.Responder counts include remitters.The post-treatment score was de?ned as the?rst available follow-up clinical assess-ment in the window from2to6weeks post-treatment.Patients with missing pre-treatment scores were excluded from calculating response but not remission rates.
Data analysis
Data analysis methods are described in detail in the Supplementary Material.Mixed-effects modeling,and kernel den-sity estimation of the response distributions were performed in Stata13(StataCorp,College Station,Texas,USA).False discovery rate(FDR)correction,cumulative distribution function plotting,and the Kolmogorov e Smirnov and Shapiro e Wilk testing of the response distributions(in cases of non-normality)were calculated in MATLAB(Mathworks,Natick,Massachusetts,USA).All data are presented as mean?standard deviation.
Results
Demographic and clinical characteristics
A total of185patients underwent DMPFC-rTMS during the de?ned period(10Hz,n?98;iTBS,n?87).The groups showed no differences in proportion of males versus females,proportion of unipolar versus bipolar illness,pre-treatment severity of illness on HamD17or BDI-II,length of current episode,number of previous episodes,or number of previous medication trials(Table1).How-ever,iTBS patients were signi?cantly older than10Hz patients (10Hz,38.4?12.6;iTBS,45.9?13.2;t183?3.99,P?0.001,FDR-corrected).
rTMS treatment parameters
Treatment parameters are summarized in Table1.The total number of stimulation runs performed in this series was7912, applied bilaterally during3956sessions,in185unique patients (10Hz:4274runs,2137sessions,98patients;iTBS:3638runs,1819 sessions,87patients).Overall mean course length was21.4?4.7 sessions,with no signi?cant difference between groups(10Hz, 21.8?4.3;iTBS,20.9?5.1;t183?1.33,P?0.183).Expressed in terms of maximum stimulator output,the mean stimulation in-tensity(120%of resting motor threshold)did not differ signi?cantly between groups for either left DMPFC(10Hz,64.6%?11.2%;iTBS, 65.1%?10.3%;t183?0.35,P?0.724)or right DMPFC(10Hz, 64.5%?11.0%;iTBS65.0%?10.3%;t183?0.29,P?0.770).
Safety and tolerability
No seizures or other serious adverse events occurred in any patient during the period reviewed.Con?dence interval estimation (via the adjusted Wald method)yields an estimated incidence rate range for seizure or other serious adverse events at0.0002per stimulation run(95%con?dence interval(CI),0e0.0008),0.0005 per session(95%CI,0e0.0015),and0.010per patient(95%CI, 0e0.323)for10Hz DMPFC-rTMS.For iTBS,the corresponding es-timates are0.0003per stimulation run(95%CI,0e0.0009),0.0005 per session(95%CI,0e0.0018),and0.011per patient(95%CI, 0e0.362).
The all-causes premature discontinuation rate for10Hz stimu-lation was6of98patients(6.1%).1patient quit at10sessions due to intolerable headaches,2patients quit at18sessions and2at19 sessions due to lack of response,and1at14sessions due to excessive commute time to the clinic.The all-causes premature discontinuation rate for iTBS was12of87patients(13.8%).2pa-tients quit at9and16sessions for intolerable headache,1at11 sessions for intolerable vertigo,1at19sessions due to mood improvement complicated by increasingly hostile thoughts toward co-workers(but no manic symptoms),2at11and19sessions for lack of response,3at4,10,and11sessions due to excessive commute time,2at16and18sessions after achieving satisfactory gains,and1for reasons unspeci?ed.The proportion of patients discontinuing due to adverse symptoms,lack of response,or un-speci?ed reasons did not differ signi?cantly between groups(10Hz, 5/98;iTBS,7/87;P?0.552,Fisher’s exact test).The proportion of patients discontinuing due to any adverse symptom(headache/ vertigo/hostility)also did not differ signi?cantly between groups (10Hz,1/98;iTBS,4/87;P?0.189,Fisher’s exact test).
Treatment ef?cacy e dichotomous outcomes
Among patients for whom HamD17data was available,in the 10Hz group,42/83(50.6%)achieved response and37/96(38.5%) achieved remission.In the iTBS group,32/66(48.5%)achieved response and24/86patients(27.9%)achieved remission.Among patients with BDI-II data,in the10Hz group,39/96(40.6%)ach-ieved response and28/96(29.2%)achieved remission.In the iTBS group,37/86(43.0%)achieved response and27/87patients(31.0%) achieved remission.There was no signi?cant difference in rates of response or remission between groups on either measure(Table2).
Combining available data from both groups,on the HamD17,74/ 149(49.7%)achieved response,and61/182(33.5%)achieved remission overall.On the BDI-II,76/182(41.8%)achieved response
N.Bakker et al./Brain Stimulation8(2015)208e215 210
and55/183(30.1%)achieved remission overall.Denominator vari-ations above re?ect missing values.
Treatment ef?cacy e continuous outcomes
On the HamD17,symptoms improved from22.4? 6.5to 12.3?8.9(decreasing44.3%?35.5%)in the10Hz group and from 21.1?5.1to12.7?7.9(decreasing43.6%?35.6%)in the iTBS group (Fig.1A).The mixed-effects model revealed a signi?cant main effect of time(z?à5.90,P<0.001)but not of group(z?à0.01, P?0.994).Notably,the group by time interaction was non-signi?cant(z?à0.72,P?0.473).There was also no signi?cant difference in pre-treatment,post-treatment scores or percent improvement between groups(Table3).
Likewise,on the BDI-II,symptoms improved from35.3?10.8to 22.4?15.5(decreasing38.4%?36.6%)in the10Hz group and from 35.9?9.9to20.2?13.3(decreasing42.6%?32.2%)in the iTBS group(Fig.1B).Here again,the mixed-effects model revealed a signi?cant main effect of time(z?à9.02,P<0.001)but not of group(z?0.11,P?0.910).The group by time interaction was also non-signi?cant(z?1.84,P?0.066)and trending in favor of iTBS over10Hz stimulation.There was no signi?cant difference in pre-treatment,post-treatment BDI-II scores or percent improvement between groups(Table3).
On further examination,the Shapiro e Wilk test revealed a signi?cantly non-normal distribution of outcomes in both the10Hz group(HamD17:W?0.958,P?0.010;BDI:W?0.973,P?0.042) and the iTBS group(HamD17:W?0.969,P?0.093;BDI:W?0.957, P?0.007);the HamD17distribution in the iTBS group trended to-ward non-normality without reaching signi?cance.On inspection of the kernel density estimates for each group and each measure, the distribution appeared trimodal in most cases,with a distinct non-responder and responder subgroup as well as intermediate, partial responder subgroup(Fig.2).
In light of the non-normal distributions of outcomes,we also performed a non-parametric(two-sample Kolmogorov e Smirnov) comparison of the cumulative distribution functions for the degree of improvement across all subjects in each group.Once again,there was no signi?cant difference between10Hz and iTBS outcomes on either the HamD17(D?0.07,P?0.991)or BDI-II(D?0.108, P?0.646)(Fig.3).
Finally,due to the non-normal distributions of outcomes,in order to rule out the possibility of subtle differences in the effec-tiveness of10Hz versus iTBS that might be apparent in responders alone,we separated the responder and non-responder individuals, then repeated the mixed-effects model analysis using only the responder patients(Fig.4).Once again,on the HamD17,the responder subgroup showed a signi?cant main effect of time (z?à7.70,P<0.001)but not of group(z?à1.00,P?0.316),and the group by time interaction was also non-signi?cant(z?à0.11, P?0.914).On the BDI-II,the responder subgroup showed a sig-ni?cant main effect of time(z?à10.4,P<0.001),and a signi?cant main effect of group with the iTBS group showing slightly more severe illness in general(z?à2.05,P?0.041).Here the group by time interaction showed a small but signi?cant effect in favor of iTBS over10Hz stimulation(z?2.35,P?0.019).
Predictors of outcome
Demographic,clinical,and rTMS parameter predictors of outcome are presented in Table4.Neither the10Hz group,nor the iTBS group,nor the combined set of both groups showed any sig-ni?cant correlation(post-FDR-correction)between percent improvement on the HamD17and any of the following variables: age,sex,unipolar/bipolar illness,pre-treatment HamD17or BDI score,length of current episode,number of previous episodes, number of previous medication trials,number of treatment ses-sions,or stimulation intensity.We also examined each individual item on the pre-treatment HamD17and BDI-II scales for correlation to improvement on the HamD17post-treatment(Tables S1e S3, Supplementary Material).Across all patients,only BDI-Pessimism (P?0.047)and BDI-Indecisiveness(0.024)signi?cantly correlated to HamD17outcome following FDR-correction.
Discussion
To our knowledge,this case series of185patients is the largest thus far reported for patients receiving DMPFC-rTMS for a major depressive episode.Consistent with our?rst hypothesis,both iTBS and10Hz stimulation appear to be safe and well tolerated,with no serious adverse events in>7900stimulation runs,and no
Table1
Demographic and clinical characteristics and treatment parameters for patients undergoing10Hz and iTBS DMPFC-rTMS.
Overall10Hz iTBS t P P(FDR)
Total sessions395621371819e e e
#patients1859887e e e Female1277057e0.4290.770 Bipolar291712e0.5490.770 Age41.9?13.438.4?12.645.9?13.2 3.99>0.0010.001 Pre-treatment HamD1721.7?6.222.1?6.921.1?5.1 1.030.3030.770 Pre-treatment BDI-II35.6?10.435.4?10.835.9?9.90.340.7330.770 Length of current episode(months)41.4?61.239.8?53.142.9?68.10.310.7550.770
#previous episodes 4.6?8.8 4.1?8.3 4.9?9.20.400.6890.770
#previous medication trials 6.2?3.9 5.9?3.9 6.5?3.90.890.3750.770
#sessions/course21.4?4.721.8?4.320.9?5.1 1.330.1840.770 Stimulation intensity(Left)64.8%?10.8%64.6%?11.2%65.1%?10.3%0.350.7240.770 Stimulation intensity(Right)64.8%?10.6%64.5%?11.0%65.0%?10.3%0.290.7700.770
FDR,false discovery rate;iTBS,intermittent theta burst stimulation;HamD17,17-item Hamilton Depression Rating Scale;BDI-II,Beck Depression Inventory-II.
Values indicate mean?standard deviation.P-values are for two-sample t-statistics for continuous variable comparisons and for Fisher’s exact test for proportion comparisons.
Table2
Dichotomous outcomes for patients undergoing10Hz and iTBS DMPFC-rTMS.
Overall10Hz iTBS P
HamD17
Response74/149(49.7%)42/83(50.6%)32/66(48.5%)0.869
Remission61/182(33.5%)37/96(38.5%)24/86(27.9%)0.157
BDI-II
Response76/182(41.8%)39/96(40.6%)37/86(43.0%)0.765
Remission55/183(30.1%)28/96(29.2%)27/87(31.0%)0.872
FDR,false discovery rate;iTBS,intermittent theta burst stimulation;HamD17,17-
item Hamilton Depression Rating Scale;BDI-II,Beck Depression Inventory-II.
P-values are for Fisher’s exact text comparing the10Hz and iTBS outcomes.
N.Bakker et al./Brain Stimulation8(2015)208e215211
signi ?cant differences between groups in rates of discontinuation due to adverse effects.The safety pro ?le of iTBS is particularly notable given that it was administered at the same stimulation intensity as 10Hz rTMS:120%of resting motor threshold for lower extremity movements.Not only is the motor threshold for the lower extremity approximately some 50%higher than for the upper extremity,but the multipliers commonly used for iTBS are also typically much lower:i.e.,80%of active (not resting)motor threshold [16,17,25,26].This much lower intensity was also used in the most recent trials of TBS targeting DLPFC in major depression [20,21].However,the absence of seizures or other adverse events,and equivalent tolerability across 3638runs of stimulation in 87individuals suggests that iTBS might be safely performed at the same intensity as 10Hz stimulation,at least for the DMPFC target.
Regarding effectiveness,in keeping with our second hypothesis,iTBS matched or exceeded the effectiveness of 10Hz stimulation on
both clinician and self-rated measures,despite requiring 5-fold fewer pulses and time to administer.The pace of improvement over time was also equal (or signi ?cantly better)for iTBS versus 10Hz stimulation.Although patients were not prospectively ran-domized in this naturalistic series,there were no signi ?cant dif-ferences in demographic or clinical characteristics between groups,aside from higher age in the iTBS group.Thus,it is unlikely that the equivalent effectiveness of iTBS in this series can be accounted for solely in terms of less severe or less refractory illness in the iTBS versus the 10Hz group.
As hypothesized,the distribution of outcomes was signi ?cantly non-normal on 3out of the 4plots and trending to non-normality on the fourth.Although our previous study of 10Hz DMPFC-rTMS found a bimodal outcome distribution [11],the present series identi ?ed a more complex response distribution,appearing closer to trimodal across all 4combinations of measures and interventions.In addition to responder and non-responder subgroups,each of the kernel density estimates revealed signs of an intermediate “partial responder ”group,with a peak around 50e 60%improvement,more apparent on self-report than clinician ratings (Fig.2).
We have previously found that the response to 10Hz DMPFC-rTMS could be predicted by anhedonia-related symptoms:pessi-mism,loss of pleasure,and loss of interest [11].In this larger series,only BDI-Pessimism and BDI-Indecisiveness showed a signi ?cant correlation to HamD 17outcome in the combined sample after correction for multiple comparisons (Supplementary Tables S1e S3).No single item,and no clinical or demographic feature,signi ?cantly predicted outcome in both groups independently.Thus,this larger sample did not con ?rm the utility of anhedonia symptoms,or any other clinical features,for predicting treatment outcome across 10Hz or iTBS DMPFC-rTMS independently.
The original rationale for pursuing rTMS of the DMPFC rather than the conventional DLPFC was to achieve better outcomes by targeting a region potentially more central to depression patho-physiology [7,27e 29].However,the present case series yielded overall response and remission rates of 49.7%and 33.5%(HamD 17),and 41.8%and 30.0%(BDI-II).These rates are not,in fact,superior to rates reported in other open-label series using DLPFC-rTMS:41.2%and 35.3%in n ?85[4],51.6%and 34.4%in n ?93[3],41.0%and 30.5%in n ?141[22],and 58.0%and 37.1%in n ?307[2].This may indicate that DMPFC-rTMS offers no ef ?cacy advantages over
Table 3
Continuous outcomes for patients undergoing 10Hz and iTBS DMPFC-rTMS.
10Hz
iTBS
t
P
All patients
Pre-treatment HamD1722.1?6.921.1?5.1 1.030.303BDI-II
35.4?10.835.9?9.90.340.733Post-treatment HamD1712.3?8.912.7?7.90.320.750BDI-II
22.4?15.520.2?13.3 1.030.307%improvement HamD1744.3%?35.5%43.6%?35.6%0.120.905BDI-II
38.4%?36.6%
42.6%?32.2%
0.82
0.415
Responders only Pre-treatment HamD1720.8?6.921.3?4.90.350.729BDI-II
32.0?11.236.5?8.0 2.010.049Post-treatment HamD17 5.7?3.8 6.0?3.90.330.740BDI-II
14.1?10.911.3?7.6 1.290.200%improvement HamD1771.4%?18.2%72.4%?16.2%0.250.807BDI-II
55.4%?29.3%
67.9%?22.3%
2.08
0.041
FDR,false discovery rate;iTBS,intermittent theta burst stimulation;HamD17,17-item Hamilton Depression Rating Scale;BDI-II,Beck Depression Inventory-II.Values indicate mean ?standard
deviation.
Figure 1.Change in symptom severity over the course of treatment for patients receiving DMPFC-rTMS,using a 30-min 10Hz (n ?98,blue)or a 6min iTBS (n ?87,red)protocol,on the HamD17(A)and the BDI-II (B)symptom scales.Mixed-effects modeling revealed a signi ?cant main effect of time (P <0.001)but not of group (P ?0.994),and no signi ?cant group by time interaction (0.473)on the HamD17.The same was true for the main effect of time (P <0.001),group (P ?0.910),and the group by time interaction (P ?0.066)on the BDI-II.HamD17,17-item Hamilton rating scale for depression;BDI-II,Beck Depression Inventory-II.iTBS,intermittent theta burst stimulation.
N.Bakker et al./Brain Stimulation 8(2015)208e 215
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DLPFC-rTMS.Alternatively,broad access to treatment in this series may have allowed inclusion of patients with more refractory illness.It is also possible that DMPFC-rTMS and DLPFC-rTMS treat two different but roughly equal-sized subpopulations of MDD patients.Resolution of these issues must await a randomized trial comparing the two techniques directly.
The present report carried several important limitations.First,patients were not allocated randomly or prospectively,leaving open the possibility that some systematic allocation bias may have made the treatments appear more similar in ef ?cacy than they are in reality.Second,the target of stimulation was the DMPFC rather than the standard DLPFC,leaving open the possibility that the ?ndings may not generalize to the much more widely used DLPFC target.Likewise,because of the insuf ?cient number of patients receiving DLPFC stimulation at the clinic during the reviewed period,the present study does not allow for a comparison of outcomes for DLPFC-versus DMPFC-rTMS,whether unilateral or bilateral.Finally,the patient sample in this study was more broadly inclusive than in most randomized controlled trials of rTMS.Although the broad inclusion criteria were intended to make the ?ndings more gener-alizable to real-world practice,the resultant heterogeneity may have obscured some potentially relevant predictors of outcome.Thus,in a more clinically homogenous sample,several of the clin-ical,demographic,and symptom items surveyed in this study could prove to be more reliable outcomes predictors.In particular,the lack of a structured assessment of medication resistance (e.g.,the Antidepressant Treatment History Form)in the available clinical data may have obscured the role of medication resistance
in
Figure 2.Kernel density estimates of the distributions of outcomes (expressed as percentage improvement from pre-treatment to ?rst post-treatment follow-up)in patients receiving 10Hz stimulation on HamD17(A)and BDI-II (B)measures,and in patients receiving iTBS on HamD17(C)and BDI-II (D)measures.HamD17,17-item Hamilton rating scale for depression;BDI-II,Beck Depression Inventory-II.iTBS,intermittent theta burst
stimulation.
Figure 3.Empirical cumulative distribution function plots comparing the outcomes (expressed as percentage improvement from pre-treatment to ?rst post-treatment follow-up)in patients receiving 10Hz stimulation versus iTBS on HamD17(A)and BDI-II (B)measures.Kolmogorov e Smirnov test revealed no signi ?cant differences in these distributions on either the HamD17(P ?0.991)or the BDI-II (P ?0.646).HamD17,17-item Hamilton rating scale for depression;BDI-II,Beck Depression Inventory-II.iTBS,intermittent theta burst stimulation.
N.Bakker et al./Brain Stimulation 8(2015)208e 215213
predicting outcome.Previous authors have identi ?ed a variety of DLPFC-rTMS outcome predictors:age and number of previous failed medication trials [30],episode duration [31],extraversion [32],sleep disturbance [33],apathy symptomatology [34],and HamD 17items for depressed mood and guilt [35].A prospective study with more rigidly de ?ned inclusion criteria,and more structured assessment of medication resistance,could reveal whether these predictors apply to DMPFC-rTMS as well.
Regarding future directions,the present ?ndings are supportive for proceeding to a randomized trial comparing 3min iTBS to the standard 37.5min 10Hz protocol [14,15]at the conventional left DLPFC target.Even if iTBS proved merely non-inferior to conven-tional stimulation,this would still allow up to a ?ve-fold increase in capacity and decrease in cost-per-session,on existing infrastruc-ture.iTBS could potentially reduce the cost of rTMS to under $1000for 20sessions,while expanding the capacity of each clinic to >25patients/device/day.Less expensive,higher-throughput protocols would constitute a major step forward toward widespread adoption of rTMS as a mainstream alternative/adjunct to medications and psychotherapy in MDD patients.
Another important follow-up study would involve a randomized comparison of DMPFC and DLPFC stimulation.Ideally,such a study would characterize individual patients as comprehensively as
possible prior to treatment,using clinical and behavioral measures as well as biological markers such as neuroimaging,electrophysi-ological,and genomic studies.These data would be essential for addressing whether DLPFC-and DMPFC-rTMS treat similar or distinct subpopulations of MDD patients.If the latter case,these data could also prove useful in identifying predictive biomarkers to guide the choice of stimulation target in individual patients pre-senting for rTMS treatment.Conclusions
The parameters of rTMS are still being optimized,nearly 20years after the ?rst use of the technique.The present study suggests that DMPFC-rTMS can be performed safely and tolerably at high stimulation intensities,and that 3min iTBS protocols may match the ef ?cacy of much longer 10Hz protocols.The overall effective-ness of DMPFC-rTMS appears comparable to,but not markedly superior to,standard DLPFC-rTMS.Randomized trials comparing iTBS versus 10Hz stimulation,and DMPFC-versus DLPFC-rTMS,will provide a more rigorous test of which techniques can achieve optimal outcomes,both in MDD in general,and in individual patients.
Acknowledgments
The authors wish to thank Aisha Dar,Vanathy Niranjan,and Dr.Umar Dar for technical assistance with rTMS delivery and data collection.
Supplementary data
Supplementary data related to this article can be found at https://www.doczj.com/doc/c715360333.html,/10.1016/j.brs.2014.11.002.References
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Figure 4.Change in symptom severity over the course of treatment for responder patients only (!50%improvement),using a 30-min 10Hz (n ?98,blue)or a 6min iTBS (n ?87,red)protocol,on the HamD17(A)and the BDI-II (B)symptom scales.Mixed-effects modeling revealed a signi ?cant main effect of time but not of group,and no signi ?cant group by time interaction,on the HamD17.On the BDI-II,there was a signi ?cant effect of time (P <0.001),and of group (P ?0.041)with more severe illness in the iTBS group,and a signi ?cant group by time interaction favoring iTBS over 10Hz rTMS (P ?0.019).HamD17,17-item Hamilton rating scale for depression;BDI-II,Beck Depression Inventory-II.iTBS,intermittent theta burst stimulation.
Table 4
Demographic,clinical and treatment parameter predictors of outcome.
10Hz iTBS All patients r
P r P r P Age >0.0010.9980.2230.0720.0910.272Female à0.0080.9460.1600.1990.0690.405Bipolar
0.0830.456à0.0280.8210.0390.633Pre-treatment HamD 17à0.0890.4260.0300.811à0.0420.612Pre-treatment BDI-II
à0.2750.012à0.0380.763à0.1760.032Length of current episode à0.1990.1180.0500.705à0.0620.500#previous episodes
à0.2100.2330.1540.3140.0820.474#previous medication trials à0.0820.4830.0440.752à0.0380.670#sessions
0.1130.3100.1560.2120.1330.106Stimulation intensity (left)à0.0230.837à0.0420.737à0.0310.709Stimulation intensity (right)
à0.019
0.867
à0.085
0.496
à0.048
0.568
FDR,false discovery rate;iTBS,intermittent theta burst stimulation;HamD17,17-item Hamilton Depression Rating Scale;BDI-II,Beck Depression Inventory-II.
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难治性抑郁症患者疗效的对照研究 发表时间：2015-10-19T16:30:28.600Z 来源：《河南中医》2015年6月供稿作者：陈良梅1 侯吉星2 [导读] 西安市精神卫生中心难治性抑郁症成为现在精神、心理疾病领域中人们关注的热点和重点。 陈良梅1 侯吉星2 （陕西西安市精神卫生中心陕西西安 710061） 【摘要】目的：探讨认知心理治疗对难治性抑郁症患者的疗效，试图为难治性抑郁症患者找到可以治疗的方法。方法：选取60例难治性抑郁症患者，将这60例患者随机分为两组，每组30例。一组单纯采用心理治疗，另一组采用文拉法辛缓释片药物合并心理治疗。分别治疗8周时间，采用汉密尔顿抑郁量表（HAMD）17项、Montgomery-Asberg 抑郁量表（MADRS），分别对两组患者各个阶段的病情进行量表评分，然后计算出其每个阶段治疗前后的HAMD17项和MADRS减分率。最后进行t检验，比较各组之间是否有差别。结果：治疗8周后两组的HAMD17项减分率的情况：药物合并心理治疗组的减分率大于心理治疗组，二者之间有统计学上的差异，P值＜0.01；治疗8周后两组的MADRS量表减分率的情况：药物合并心理治疗组的减分率大于心理治疗组，二者之间有统计学上的差异，P值＜0.01。结论：药物合并心理治疗对难治性抑郁症效果优于单纯的心理治疗，对于难治性抑郁症的治疗可以采用药物治疗合并心理治疗。 【关键词】难治性抑郁症；认知心理治疗；药物联合心理治疗 【中图分类号】R749.4 【文献标识码】B 【文章编号】1003-5028（2015）6-0573-02 The study of efficacy about Cognitive therapy for patients with refractory depression. CHEN Liang-mei, HOU jixing. Xi'an Mental Health Center, Xi an 710061, China. 【Abstract]】Objective：To investigate the efficacy about the cognitive psychotherapy in patients with refractory depression, and trying to find the treament methods of patients with refractory depression.Methods：Selected 60 cases of patients with refractory depression, these 60 patients were randomly divided into two groups of 30 patients. A group of only was treated using psychotherapy, and the other group was treated with venlafaxine plus drugs combined psychotherapy. After 8 weeks, respectively, using the Hamilton Depression Rating Scale17 items (HAMD17), Montgomery-Asberg Depression Rating Scale (MADRS), respectively, two groups of patients for the various stages of illness scale score, and then calculates each of its stages before and after treatment the HAMD17 and MADRS reduced rate. Finally, t-test to compare whether there is a difference between the groups. Results：After 8 weeks of treatment in each group HAMD17 reduction rate case: Drugs in combination with psychological therapy group reduced rate greater than psychotherapy group, and statistically significant difference between, P<0.01. After 8 weeks of treatment in each group MADRS-scale reduction rate case: Drugs in combination with psychological therapy group reduced rate greater than psychotherapy group, and statistically significant difference between, P<0.01. Conclusions：Drug therapy combined psychological refractory depression better than a single psychotherapy. For the treatment of refractory depression can be treated with medication combined psychotherapy. 【Key Words】Refractory depression；Psychological treatment；drugs combined psychotherapy. 难治性抑郁症成为现在精神、心理疾病领域中人们关注的热点和重点。因为难治性抑郁症是临床上比较难处理的棘手问题，近年来有人试图找到对其有效的治疗方案，但这类的研究目前还很少。有研究表明，难治性抑郁症患者除了临床抑郁症状外，还存在着认知功能的障碍，以及心理方面认知上的偏差。既然如此，心理治疗可能对难治性抑郁症患者有效。本研究采用随机对照的研究方法，试图找出认知心理治疗对难治性抑郁症患者的疗效。 1 研究方法： 1.1 研究对象： 选取了60例西安市精神卫生中心在2010年9月~2014年3月住院或门诊的难治性抑郁症患者。 研究组入组标准：（1）年龄18~65岁，男女均可；（2）符合ICD--10抑郁症的诊断标准，经过两种以上不同类型的抗抑郁药物足量足疗程治疗，现在仍符合抑郁症诊断的患者；（3）汉密尔顿抑郁量表（HAMD）17项总分≥18分；（4）无严重躯体及脑器质性疾病；（5）小学文化程度以上，能配合完成认知心理治疗者；（6）患者及家属知情同意。 1.2 研究方法： 将60例难治性抑郁症患者随机分为两组，每组30例，A组：单纯采用心理治疗，B组：采用文拉法辛缓释片药物合并心理治疗。两组均进行治疗8周时间，采用汉密尔顿抑郁量表（HAMD）17项、Montgomery-Asberg 抑郁量表（MADS）进行评分，分别对两组在基线、治疗4周末、治疗8周末的病情进行量表评分，然后计算出其每个阶段的HAMD17项和MADS减分率:（各时点的量表评分—基线量表评分）/基线量表评分。 1.3 研究步骤： （1）按照研究标准选择入组人员：难治性抑郁症患者； （2）向入组人员详细讲解研究目的和注意事项，并征得病人的同意，要求患者按照要求完成药物或者心理治疗，以及量表评定； （3）将获得的研究资料进行统计分析。 1.4 资料分析： 将所有资料输入计算机，建立数据库，采用SPSS 15.0统计软件包进行数据统计分析，t检验，显著性水平为P值＜0.05，比较两组之间是否有差别。 2 结果： 2.1 一般资料： 研究组60例，平均年龄（31.7±9.7）岁，男性26例，女性34例，平均接受教育（12.5±4.8）年，入组时HAMD17项总分为 （26.74±3.83）分，MADS总分（22.56±2.72）分。 基线时：A、B组的HAMD17项评分，A组（26.87±3.65）分，B组（27.56±2.45）分；A、B组的MADS评分，A组（22.45±3.12）分，B组（21.56±2.84）分。
一般心理问题、严重、神经症性与神经症的区别： 一般心理问题、严重心理问题、神经症性心理问题与神经症的区别： （一）、一般心理问题 诊断为一般心理问题须满足条件：现实因素激发、持续时间较短、不严重影响社会功能、情绪反应没有泛化。 1．现实因素激发——因 由于现实生活、工作压力、处事失误等因素而产生内心冲突，并因此体验到不良情绪。（常形冲突） 2．持续时间较短——时 不良情绪不间断持续满1个月或不良情绪间断地持续2个月仍不能自行化解。（不是心理冲突持续） 3．社会功能常态——度 不良情绪反应仍在相当程度理智控制下，人格没有明显异常，行为不失常态，生活学习社交基本正常，但效率下降。 4．反应没有泛化 自始至终，不良情绪的激发因素仅仅局限于最初事件；即便是与最初事件有联系的其他事件，也不引起此类不良情绪。 （二）、严重心理问题
诊断为严重心理问题，必须满足如下条件：强烈刺激、时间持久、反应强烈、反应泛化。 1．强烈刺激——因 引发原因是较为强烈的、对个体威胁较大的现实刺激。求助者体验着痛苦情绪。（没有引发心理冲突，而是直接导致痛苦情绪） 2．时间持久——时 痛苦情绪间断或不间断地持续时间在2个月以上，6个月以下。 3．功能受损——度 遭受的刺激强度越大，反应越强烈。 （1）多数情况下，会短暂地失去理性控制； （2）在后来的持续时间里，痛苦可逐渐减弱，但单纯依靠自然发展或非专业性干预难以解脱； （3）社会功能受损——对生活、工作和社会交往有一定程度影响。4．反应泛化 痛苦情绪不但能被最初的刺激引起，而且与最初刺激相类似、相关联的刺激，也可以引起此类痛苦，即情绪反应对象被泛化。 （三）、神经症性心理问题 神经症性心理问题即可疑神经症，还没有把握诊断是还是不是神经症，但可以给予可疑诊断。 神经症性心理问题从五个方面诊断：心理冲突、持续时间、精神痛苦、症状泛化、功能受损。 1．变形冲突——因
艾司西酞普兰合并无抽搐电休克治疗难治性抑郁症对照研究 发表时间：2012-02-01T11:42:00.090Z 来源：《中外健康文摘》2011年第39期供稿作者：李强鲁美玲李潇 [导读] 抑郁症（MD）是一种常见的情感性疾病，多呈慢性复发性病程，对患者的社会功能有较大影响。 李强鲁美玲李潇（山东威海经济技术开发区医院临床心理科山东威海 264200） 【中图分类号】R749.1【文献标识码】A【文章编号】1672-5085（2011）39-0040-02 【摘要】目的探讨无抽搐电休克（MECT）合并艾司西酞普兰治疗难治性抑郁症的疗效与安全性。方法 60例难治性抑郁症患者随机分为研究组（MECT合并艾司西酞普兰组）与对照组（单用艾司西酞普兰组）。每组均为30例。观察4周。采用汉密尔顿抑郁量表及焦虑量表、临床疗效总评量表、副反应量表评定临床疗效及副反应。结果根据HAMD、HAMA评分，研究组在1周末、2周末、4周末显效率明显高于对照组，差异有显著性（P<0.05或P<0.01）。两组TESS评分无差异。结论无抽搐电休克合并艾司西酞普兰治疗难治性抑郁症具有起效快，疗效好，不良反应轻微的优点，值得临床推广应用。 【关键词】无抽搐电休克难治性抑郁症艾司西酞普兰脑源性神经营养分子药物治疗 抑郁症（MD）是一种常见的情感性疾病，多呈慢性复发性病程，对患者的社会功能有较大影响。大多数抑郁症患者可用药物及配合心理治疗达到临床治愈，但有20%～30%的病例对各种治疗没有反应，成为难治性抑郁症，故难治性抑郁症是一重要的临床课题。为讨论MECT合并艾司西酞普兰治疗难治性抑郁症的疗效及安全性，我们进行了如下研究并报道如下。 1 对象与方法 1.1对象为2009年10月～2011年7月在我院门诊或住院治疗的60例难治性抑郁症患者。符合以下标准：①年龄18～65岁；②符合难治性抑郁症的标准：a.符合CCMD－3抑郁发作的诊断标准；b.本次发作至少两种作用机制不同抗抑郁药经足量、足程治疗无效或收效甚微。 ③无MECT禁忌症。④排除严重躯体疾病、双相障碍、快速循环发作、酒精和药物依赖者、患者同意接受MECT和药物治疗。⑤血尿常规，肝肾功能，心电图及胸透和头颅CT均正常。严重睡眠障碍者可加佐匹克隆7.5mg睡前服。 按照入组时间先后顺序随机分为MECT合并艾司西酞普兰（研究组）、单用艾司西酞普兰组（对照组）。研究组30例，男16例，女14例。年龄22～60岁，平均（38.61±15.23）岁。本次病程6～33周，平均（15.17±13.92）周；入组时HAMD评分（35.39±13.74），HAMA 评分（23.07±6.18），CGI评分（5.98±1.11）。对照组30例，男14例，女16例。年龄29～63岁，平均（40.27±16.73）岁，本次病程6～35周，平均（15.76±14.31）周；入组时HAMD评分（34.13±13.01），HAMA评分（22.93±5.71），CGI评分（5.76±1.17）。两组比较差异均无显著性（P＞0.05）。 1.2治疗方法研究组MECT每周二、四、六上午进行，10～12次为一个疗程，由于行MECT治疗前需空腹，因此每日中午服用艾斯西酞普兰，起始剂量5mg/日，之后根据耐受情况和不良反应情况，于2周内加至10-20mg/日（平均11.93±4.01mg/日）；对照组同样加药方式（平均1 2.41±4.25mg/日）。两组药物剂量无差异（P>0.05），严重睡眠障碍者可加佐匹克隆7.5mg／晚。总疗程4周。 1.3观察指标疗效和副反应采用HAMD、HAMA、CGI、TESS,在入组时及治疗第1、2、4周末各评定一次。疗效按四级评定标准进行临床疗效评定。HAMD减分率≥75﹪为痊愈，50%～74%为显效，25%～49%为好转，＜25%为无效。各量表为两名主治医师评定，评定者的一致性检验Kappa≥0.83。实验室及辅助检查包括血常规、肝功、电解质、心电图等于入组、结束时各检查一次。 1.4统计方法将以上数据输入SPSS17.0 for windows软件进行处理，组间比较采用t检验。 2 结果 2.1两组治疗前后HAMD分值比较治疗后第1周末研究组HAMD分明显下降（与治疗前比较P<0.01），表明治疗已经起效，而对照组变化不明显（与治疗前比较P>0.01）。治疗第4周末，HAMD评分研究组明显低于对照组，且有极显著性差异（P＜0.05），说明研究组疗效明显优于对照组，起效较快。 2.2两组治疗前后HAMA分值比较研究组第1周末与治疗前HAMA分值比较就有显著性差异（P＜0.01），而第二组至第2周末与治疗前HAMA分值比较仍P>0.05，而从第1周末开始研究组HAMA分值明显低于对照组（组间比较P<0.01）,说明MECT合并艾司西酞普兰治疗焦虑症状起效快、疗效显著。 2.3安全性分析两组治疗后TESS比较差异无显著性（P＞0.05）。两组不良事件发生频率相当，多为口干、便秘、胃部不适等。严重程度多为轻度，未予特殊处置。试验期间没有严重的不良事件发生。研究组在第一次MECT治疗后多数患者都有头痛、嗜睡的反应，无需特殊处理，数小时后自行缓解。此外，研究组有记忆力差的副反应，多数患者在停止MECT治疗后数周内好转。实验室检查：两组在治疗前后均无临床意义的异常变化。 2.4临床疗效评定两组4周末评定，研究组显效17例，有效10例，无效3例，显效率56.67%；对照组显效7例，有效6例，无效7例，显效率2 3.33%。两组比较差异有显著性（P＜0.01）。 3 讨论 难治性抑郁症的诊断标准尚无统一的定义，目前较普遍的观点认为难治性抑郁症使之符合抑郁发作的诊断标准并且用至少两种作用机制不同抗抑郁药经足量、足程治疗并且依从性良好，病人无效或收益甚微者[1]，大量占抑郁症总数的1／3。Suoery等进一步提出，如果用一种抗抑郁药足量、足程且依从性良好，病仍依然无效或带药复燃，在广义上也称为难治性抑郁症。 难治性形成的原因[2]包括医源性的：如诊断误差、用药剂量不足、用药时间不足、缺乏抗抑郁药治疗的经验。病人的原因包括依从性、伴发躯体疾病。在老年患者中，抑郁症可能和早期的痴呆或隐匿性癌症有联系。疾病原因包括共患其他精神疾病、疾病的严重程度、是否存在药物滥用等。 Karege等在2002年首次证实，MD患者脑源性神经营养因子的水平低于正常对照组，MD患者的蒙哥马利—阿拉伯格抑郁症等计量表（MADRS）得分与血清中的BDNF水平呈负相关，提示抑郁症状越重血清中BDAF的水平越低，抗抑郁药物可提高MD患者血清中BDNF的水平。Nibuya等在1995年和1996年做的两项研究表明，小鼠长期使用抗抑郁药物可增加海马区BDAF的表达。BDNF是神经营养因子家族的一员。抑郁症动物模型研究显示，给予BDNF可以产生抗抑郁样活性的行为。 改良电休克即无抽搐电休克（MECT）是在全身麻醉和肌肉放松的情况下，在脑内短暂的通过电流引起广泛的脑电发作，产生生理生
7种神经症的诊断 一、焦虑性神经症 1、排除精神病：根据病与非病三原则，该求助者主观客观世界统一，精神活动内在协调，人格相对稳定，说明该求助者不属于精神病。 2、症状表现：存在广泛性焦虑或发作性恐怖状态；常伴有头晕、胸闷、心悸、呼吸困难、出汗和运动型不安（根据案例中的症状写）。 3、存在变形心理冲突：内心紧张不安；预感到似乎将要发生不利情况而难于应付的不愉快情绪。 4、病程：超过3个月以上（根据孟德解析）； 5、严重程度：求助者的社会功能受到中等程度损害。 ６、心理测验结果及相关资料等支持本诊断。（如果题中给出SAS量表） 7、又根据许又新关于神经症的评分标准，该求助者在病程、内心痛苦程度、社会功能的得分≧6分，神经症的诊断成立。（可以根据题中的信息详细描述得分情况） 特殊记忆：惊恐障碍发作（急性焦虑状态）影响社会功能；20分钟自动缓解；一个月发作三次，有预期的焦虑。（根据孟德解析） 二、抑郁性神经症（参考习题集P339答案） 1、排除精神病：根据病与非病三原则，该求助者的知情意是统一、一致的；对自己的心理问题有自知力，主动求医，无逻辑思维混乱，无感知觉异常，无幻觉、妄想等精神病症状，因此可以排除精神病。（另一种写法） 2、症状表现：病前有抑郁性格；有精神因素诱发；情绪低落、兴趣下降、意志下降、焦虑、自我评价过低、绝望、有自杀倾向等（根据案例中的症状写）。 3、存在变形心理冲突：造成内心持久的痛苦，不能摆脱； 4、病程：症状持续超过3个月以上（根据黄书P98） 5、严重程度：求助者的社会功能受到中等程度损害。 ６、心理测验结果及相关资料等支持本诊断。（如果题中给出SDS量表） 7、又根据许又新关于神经症的评分标准，该求助者在病程、内心痛苦程度、社会功能的得分≧6分，神经症的诊断成立。（可以根据题中的信息详细描述得分情况） 三、强迫性神经症（参考黄书P351） 1、排除精神病，根据病与非病三原则，该求助者主观客观世界统一，精神活动内在协调，人格相对稳定，说明该求助者不属于精神病。 2、症状表现：存在强迫（洗手）的行为，（为清洗和不清洗苦恼）。 3、存在变形冲突：造成内心持久的痛苦，不能摆脱； 4、病程：症状持续时间超过3个月以上； 5、严重程度：求助者的社会功能受到中等程度损害。 ６、又根据许又新关于神经症的评分标准，该求助者在病程、内心痛苦程度、社会功能的得分≧6分，神经症的诊断成立。（可以根据题中的信息详细描述得分情况）
一例高三女生神经症性心理问题的案例报告张丽[关键词]高中生；神经症性心理问题；认知行为疗法；系统脱敏一、一般资料来访者：陈某，女，18岁，高三复习学生，出生在农村，与父母同住，有一姐姐，已结婚。父母经商，在家的时间很少，对其关心很少，家庭经济状况中等，经详细询问、调查，父母无人格障碍和其他神经症性障碍，家族无精神疾病历史。 二、个人成长史来访者属足月顺产，母亲身体健康，孕、产及哺乳期未服用特殊药物。父母亲忙于经商，多与爷爷奶奶一起生活。回忆六七岁时，一个夏天的中午，与本村的几个小朋友在村头的路边玩耍，曾经受到过一男子的惊吓，当时父母在外经商，没有跟父母说这件事。身体健康，未患过重大疾病。奶奶经常对来访者说女孩子大了要自重，不要与男孩子在一起打打闹闹，否则别人就会笑话“不正经”。陈某自我要求高，学习成绩好，自尊心强。因父母工作忙，对其心理成长方面关心得很少，所以陈某养成了凡事藏在心里，不与人交流，遇事自己拿主意、自己处理，非常独立要强的性格，对许多事情尽量做得尽善尽美。精神状态：来访者有一定害怕、紧张、担心、情绪低落等焦虑、抑郁和恐惧表现。身体状态：有出汗、失眠、心慌、发抖等躯体不适感，但体检报告均正常。社会功能：学习效率下降、人际关系紧张。心理测验结果：根据来访者以上资料的分析，选择以下心理测验：SCL-90、SDS、SAS。测验前对来访者说明测验对其心理问题诊断的意义，并征得了来访者及其家长的同意。1．SCL-90测试各因子分如下：躯体化2.6，强迫症状1.5，人际敏感2.7，抑郁2.5，焦虑3.2，敌对1.8恐怖2.8，偏执1.0，精神病性1.4，其他1.5；总分178；阳性项目数44个。躯体化、人际敏感、抑郁、焦虑、恐怖因子分明显高于常模。可以考虑筛选阳性。2．抑郁自评量表( SDS)分：粗分46分，标准分57分，提示有轻度抑郁。3．焦虑自评量表(SAS)分：粗分55分，标准分68分，提示有中度焦虑。三、主诉主诉：害怕擦黑板，一想到擦黑板就紧张、害怕、心慌、发抖，学习效率低，学习成绩下降四、观察和他人反映心理咨询师的观察：来访者衣着整洁，头发整齐，脸色稍带疲倦之意，讲话语速较快，言语流利，声音清晰，眼睛发红，意识清楚，无幻觉、妄想，无智能障碍，自知力完整，有明确的求助要求。从进入咨询室到叙述完毕，都表现得比较自如，但在谈到擦黑板、高考时，表现出明显的担忧和焦虑，手开始搓动，后背一会儿靠在椅子背上，一会儿又离开，明显不安和紧张。父母反映：高考失败对她打击很大。虽然自己主动选择复习，但这学期能看出她压力很大。最近几个月老发脾气，家人都觉得是压力大造成的，最近学习成绩不如以前，也不知道怎么回事，家人心里也很着急，但又帮不上忙。老师反映：陈某曾提出过调到复习班去，但因学校已经这样安排了，就没同意。陈某好像是很失望。这段时间学习状态不是很好，看上去很焦虑。开始学习成绩是全班第一，现在已经下降到二十多名。五、评估与鉴别诊断1．心理状态的评估：求助者有害怕、紧张、不安、情绪低落、担心、发抖、失眠等心理和躯体症状，痛苦情绪自己不能摆脱，学习效率下降。由此可判断来访者心理健康出现了问题，属于心理不健康状态。2．诊断：神经症性心理问题。3．诊断依据：(1)身体症状检查，各项结果呈阴性。(2)引起的心理冲突与现实处境没什么关系，涉及生活中不太重要的事，且不带有明显的道德色彩。 (3)痛苦情绪体验持续时间为两个月，未超过三个月。(4)精神痛苦难以自己解脱，对学习、人际交往有一定程度的影响。(5)出现了回避行为。(6)本案例虽有恐惧的症状，但持续时间较短，社会功能受损程度不重，未达到神经症的诊断标准。最终诊断为“神经症性心理问题”。 六、咨询目标的制定根据以上的评估与诊断，同来访者协商，确定如下咨询目标：1．具体目标与近期目标： (1)改变来访者错误的认知观念：“我高考失败说明自己很无能”；“我喜欢男同学是不正经，是坏女孩”。(2)消除来访者的不良情绪：日常学习中的焦虑，对擦黑板的恐惧，提高学习效率。学会在日常生活中适当运用放松技术和积极的自我对话，以降低焦虑水
如对您有帮助，可购买打赏，谢谢 生活常识分享抑郁性神经症有临床表现 导语：（1）情绪的改变：患者最突出的症状是持久的情绪低落，表现为表情阴郁，无精打采、困倦、易流泪和哭泣。患者常用郁郁寡欢、凄凉、沉闷 （1）情绪的改变：患者最突出的症状是持久的情绪低落，表现为表情阴郁，无精打采、困倦、易流泪和哭泣。患者常用郁郁寡欢、凄凉、沉闷、空虚、孤独、与他人好像隔了一堵墙之类的词来描述自己的心情。患者经常感到心情压抑、郁闷、常因小事大发脾气。在很长一段时期内，多数时间情绪是低落的，即使其间有过几天或1~2周的情绪好转，但很快又陷入抑郁。尽管如此，患者抑郁程度一般并不严重，情绪反应依然存在，几句幽默解嘲的警句，能使之破涕为笑。一场轻松的谈话，能使之心情暂时好转。患者本人也能够觉察到自己情绪上的不正常，但往往将之归咎于他人或环境。 （2）认知改变：患者对日常活动缺乏兴趣，对各种娱乐或令人愉快的事情体验不到愉快，常常自卑、自责、内疚。常感到脑子反应迟钝，思考问题困难。遇事老向坏处想，对生活失去信心，自认为前途暗淡，毫无希望，感到生活没有意义，甚至企图自杀。 （3）意志与行为改变：患者意志活动减低，很难专心致志地工作，尽管他们可能有远大理想和抱负，但很少脚踏实地去做。他们想参与社交，但又缺乏社交的勇气和信心。患者处处表现被动和过分依赖，心理上的症结在于不愿负责任。一般说，抑郁性神经症很少自杀，但也有部分患者感觉活着空虚，人生乏味，声称想死。 （4）躯体症状：约80%的病例，以失眠、头痛、身痛、头昏、眼花、耳鸣等躯体症状为主向医生求助。这些症状往往给人体诉多而易变的感觉，在些症状可以长期存在，但无明显加重或缓解。这些症状
难治性抑郁症的发病机制 ●约15%的抑郁症患者（约30%的重度抑郁症患者对原来的一系列抗抑郁剂治疗无反应， 40%慢性抑郁症缺乏反应）最终转化为难治性抑郁症(treatment-resistant depressionTRD)。 ●TRD 的定义多种多样 1995年 1、对于剂量和疗程没有进行明确规定； 2、认为同一作用机制内换药的效果比不同作用机制之间换药差, 但目前尚未得出一致性结论; 3、其观点认为三环类药物优于SSRI 类药物、单胺氧化酶抑制剂优于三环类和SSRI 类太绝对; 4、没有考虑增效及合并方案的应用。 TRD ●1999年 Souery 模式 ●如果用2种不同种类的抗抑郁药足量、足程（6-8周）治疗且依从性良好，病人依然无 效称为难治性抑郁症;根据持续时间，又分为难治性抑郁（一年以内）及慢性难治性抑郁（一年以上）
●2003年 ●麻省医院(MGH)这种方法考虑到了治疗失败次数和治疗方案的优化及强度, 但它不是把 难治程度进行分层, 而是制定成了一个连续变量, 其评分与难治程度呈正比。 TRD ●评价量表：目前有三种：医生评定的为the Antidepressant Treatment History Form; the Harvard Antidepressant Treatment History,自我评定的为麻省医院 (MGH)Antidepressant Treatment Response Questionnaire (ATRQ)灵敏度75%，特异度100%。但样本量少。 TRD发病机制 ●难治性抑郁症是当今精神医学界的重要难题之一，其致病机制尚不明确，目前普遍认为， 生化、遗传、内分泌、免疫、心理社会因素及解剖结构异常等可能共同导致抑郁障碍。 单胺能假说 ●上个世纪50年代，临床偶然发现单胺类递质耗竭用药利血平在治疗高血压的同时会导 致15%的病人出现抑郁症表现;而同样的，治疗肺结核的药物因为阻断单胺类递质的降解而改善了伴发抑郁症患者的抑郁心境。 单胺能假说 ●问题： ●没有解决起效时间延迟(单胺类抗抑郁药物起效时间一般为2-4周)的问题。 ●实验性耗竭单胺类递质并不能使健康志愿者产生抑郁样情绪 ●单胺递质耗竭或者功能低下可能是初始介导者和结果之一。抗抑郁药物急性给药即刻增 加突触间隙单胺类递质浓度，而后进一步从转录和翻译水平上对下游细胞和分子的可塑
抗抑郁药 用途：临床上常用的抗抑郁药指一组用于治疗抑郁症状的精神活性药物，有时也用于治疗某些其他特定状况，如焦虑、惊恐，或强迫症状。主要分为： ①三环抗抑郁药，包括丙咪嗪，阿米替林、氯丙咪嗪及多虑平（多 塞平）等，为目前较好的抗抑郁症药，其中以阿米替林为最常 用。 ②四环抗抑郁药，临床常用的有麦普替林等，其作用和三环类相 似。 ③③选择性5-羟色胺再摄取阻滞剂（SSRI），包括氟西汀，帕罗 西汀（赛乐特）、氟伏沙明（兰释）、舍曲林（郁洛复）、文拉 法辛（博乐欣、怡诺思）等 ④单胺氧化酶抑制剂，如苯乙肼，异卡波肼，反苯环丙胺等。还 有较新推出的新型抗抑郁药，如瑞美隆等。 副作用：使人困倦、口干、视物模糊、便秘、心跳加快、排尿困难和体位性低血压，这类副作用一般不影响治疗，在治疗过程中可逐渐适应；严重的心血管副作用、尿潴留和肠麻痹少见。过量可致急性中毒甚至死亡。 一、经典抗抑郁药 1、单胺氧化酶抑制剂 异丙肼是上世纪50年代问世的第一个抗抑郁药物。异丙肼原是一种抗结核药，因有多说、多动、失眠和欣快感等中枢兴奋作用，1957
年试用于抑郁病人并获得成功。动物实验证实其可逆转利血平引起的淡漠、少动，同时，脑单胺含量升高。推测其中枢兴奋和抗抑郁作用是因为大脑单胺氧化酶受抑制单胺降解减少，使突解间隙单受含量升高的缘故。从而提示了动物行为和大脑单受类递质之间的相互关系，有着重要理论和实践意义，为精神药理和精神疾病病因学研究奠定的基础。 属于这一类的还有异卡波肼、苯乙肼、反苯环丙胺等。这些药物曾一度广为应用，不久因陆续出现与某些食物和经物相互作用，引起高血压危象、急性黄色肝萎缩等严惩不良反应而被淘汰。 80年代后期出现了新一代半日受氧化酶抑制剂，即可逆性单胺氧化酶一个亚型（MAO-A）抑郁剂，它的特点是：1对MAO-A选择性高，对另一种同功酶MAO-B选择性小，故仍可降解食物中的酷胺，从而减少高血压危象风险。2对MAO-A抑制作用具有可逆性，仅8-10小时即可恢复酶的活性，而老的半日胺氧化酶抑制剂抑制时间长达2周之久，因而也降低了与食物相互作用的危险。主要产品有吗氯贝胺，剂量150-450mg/d，分次服。据称疗效与三环类抗抑郁药相当。 虽比老的半日胺氧化酶抑制剂安全，但仍应注意体位性低血压及潜在的食物、药物间相互作用，一般也不作为首选药。 2、三环类抗抑郁药 以丙咪嗪为代表，常用的还有阿米替林。 化学结构：三环类抗抑郁药由两个苯环和一个杂环构成，咪唑类杂环上含氮，这一类衍生物较多，一般简称TCA
心理问题的划分及鉴别标准 需要区分的是： 1、重性精神病与神经症、一般心理问题、严重心理问题。区分的重点——自知力、求医行为。 2、神经症与一般、严重心理问题的区别： 区分的重点——心理冲突的性质。 2.1心理冲突有常形与变形两种。 2.2常形与变形的区分有两个标准：是否具有道德性质（是否能区分开道德与不道德）、是否与现实有直接联系。如出现第三者后，在离婚与不离婚中矛盾，这就与现实事件直接联系，并能区分开道德与非道德性质。这就是常形。如一个人整天想着是该吃饭还是不吃饭，与现实事件无直接联系，并且无法区分开道德与非道德性质。这就是变形。 2.3心理冲突如是常形，就可能是一般、严重心理问题，最多是心理障碍 2.4心理冲突如是变形，就可能是神经症。 3、一般心理问题与严重心理问题的区别： 3.1一般心理问题：符合由现实因素激发、持续时间较短（持续一个月或间断持续两个月）、 情绪反应仍在理智控制之下（始终能保持行为不失常态）、不严重破坏社会功能（效率下降）、情绪反应尚未泛化的心理状态。 3.2严重心理问题：由相对强烈的现实刺激激发、初始情绪反应强烈（靠自然发展和非专业干预难以解脱）、持续时间长久（两个月以上，半年以下）、内容充分泛化的心理不健康状态。有时伴有某一方面的人格缺陷。 4、在心理诊断中，经常会出现这样的词：非精神病性心理问题 4.1 非精神病性心理问题即是指：除了重性精神病外的心理不健康状态。包括：一般心理问题，严重心理问题和神经症性心理问题 4.2神经症性心理问题又被称为可疑神经症：第三种类型的心理不健康状态，已接近神经衰弱或神经症，或者它本身就是神经衰弱或神经症的早期阶段。有时，我们也把有严重心理问题但没有严重的人格缺点者（如均衡性较差的人格）列入这一类。 4.3因此神经症性心理问题可以总结为：可疑神经症，接近神经衰弱或神经症的早期阶段，严重心理问题但没有严重人格缺陷的求助者。接近神经衰弱或神经症的早期阶段，严重心理问题但没有严重人格缺陷的求助者。
一例高三男生抑郁性神经症心理咨询 案例报告 摘要：求助者小朱，小学、初中学习成绩在班里一直名列前茅，是家长与老师心目中的好孩子。中考时以优异的成 绩考入襄樊市某重点高中。进入高中后，成绩不如初中。经过 努力，在班上排名不升反降，居然排在倒数第五名。父母非常 生气，严厉地批评了他。他觉得自己真没用，感到父母、老师 和同学都看不起自己。一切都完了。从此觉得生活没意义，对 什么事情都不感兴趣，情绪低落、失眠、烦躁将近三年，曾想 自杀但又缺乏胆量和勇气。根据求助者小朱的自述，家长，老 师和学生们提供的情况以及我的观察，小朱的主要症状是：情 绪低落、兴趣下降、意力下降、焦虑、自我评价低、绝望、有 自杀的倾向、失眠等。对该求助者的诊断是抑郁性神经症。通 过与求助者协商和对案例的综合分析，采取合作式行为主义与 精神分析与人本主义心理咨询综合应用的方法实行心理咨询。 经过三个月十二次的心理咨询，小朱现在上课注意力很集中，学习成绩也升到班级中等水平，与同学、老师的关系正常，又 有很多兴趣和爱好了。小朱通过心理咨询已初步达到咨询的具 体目标，最终目标、短期目标和长期目标。小朱现在基本上是 一个心理健康人格完善的人了。小朱的心理咨询已完成，但效 果是否巩固需要时间考验，咨询师将实行不定期回访。精神分 析，行为主义与人本主义在心理咨询上的融合，将对心理咨询 的发展有着积极意义。 一、一般资料 小朱，男，17岁，襄樊市某重点高中高三学生，父母是老师，独生子，家庭管教很严，所以养成了内向性格。学习成绩是父母注重的重点，小学、初中学习很认真，很勤奋，是家长与老师心目中的好孩子。同学心目中的好班长，学习成绩在班里一直名列前茅。中考时
难治性抑郁症与非难治性抑郁症患者甲状腺激素水平的比较 李艾莎 【摘要】 目的 通过难治性抑郁症与非难治性抑郁症患者甲状腺激素水平的检测与比较,探讨甲状腺激素治疗难治性抑郁症的依据。方法 选取难治性抑郁症患者和非难治性抑郁症患者各32例,采用放射免疫法测定两组血清T SH,T3,FT3,T4,F T4水平。结果 难治性抑郁症组异常者18例,占56.25%,非难治性抑郁症组异常者5例,占15.63%。两组比较有统计学意义( 2= 11.47,P<0.005),难治性抑郁症患者组甲状腺激素水平异常率明显高于非难治性抑郁症组,表现为T SH上升( 2=5.13,P< 0.05),T3下降( 2=5.14,P<0.05),FT4下降( 2=5.14,P<0.05)。结论 难治性抑郁症患者中有56.25%可考虑亚临床型甲状腺功能减退,甲状腺激素合并抗抑郁药治疗难治性抑郁症是有价值的可选方案。 【关键词】 难治性抑郁症;非难治性抑郁症;甲状腺激素:甲状腺功能;抗抑郁药 Comparison on the Serum Level of Thyroid Hormone in Patients with Refractory Depression and Single Depression.L i A isha. T he Fir st Peop le's H osp ital of N eij iang City,N eij iang,S ichuan641000,P.R.China 【Abstract】 Obj ective T o investig ate fo undatio n that patients w ith r efr act or y depr ession w er e treat ed w it h t hyr oid hor mone by the detectio n and compar ison of thyr oid hor mones level of the pat ients w it h r efracto ry depressio n and sing le depr ession. Methods A t otal o f32pationts w ith refr actor y depressio n wer e measur ed fo r serum thy ro nine stimulating hor mone(T SH), to tal tr iio do thyr onine(T3),to tal thyr o xine(T4),fr ee tr iiodothy ro nine(FT3)and fr ee thy ro xine(FT4)by R adio-immunnity befor e tr eatment.Simulaneously,32single depr ession matched in sex and ag e w ere recruited as co ntro ls.Results T her e w ere 18(56.25%)patio nts with refr actor y depressio n w hose serum thy ro id hor mones lev el w as abno rmal w hich r epresented as T SH up r egulatio n( 2=5.13,P<0.05),T3( 2=5.14,P<0.05)and F T4( 2=5.14,P<0.05)dow n reg ulation,and t her e w ere only 5(15.63%)abno rma l in the co ntro ls.T here w ere sig nificant differences betw een t he t wo g r oups( 2=11.47,P<0.05). Conclusion T here is sub-clinnical thyr oid function impairment in56.25%pat ionts with r efr act or y depressio n.T hat thyr oid hor mones combined w ith ant idepr essants drugs pro vide v aluable t reat ment o ptio ns fo r the ther apy of the pat ionts w ith refr acto ry depressio n. 【Key words】 R efracto ry depressio n;Sing le depr ession;T hyr oid ho rmo ne;T hy ro id functio n;A ntidepr essant s dr ug s 我国抑郁症患病率为1.7%～2.5%[1],照此计算我国有2000～3000万抑郁症患者。在临床上虽然抗抑郁药疗效显著,但仍然有30%～50%的抑郁症患者经抗抑郁药治疗无效。临床上将经过至少2种作用机制不同的抗抑郁药足够剂量、足够疗程治疗仍然无效的抑郁症称为难治性抑郁症。目前在治疗难治性抑郁症的优化方案中有抗抑郁药合并甲状腺素治疗[2]。为了验证这个治疗方案的依据,我们分别对32例难治性抑郁症患者和32例非难治性抑郁症患者的甲状腺素水平进行了测定并进行比较。 1 对象与方法 1.1 对象 难治性抑郁症组和非难治性抑郁症组皆为2008年5月-2010年5月就诊的门诊病人,各32例。入组患者年龄为19～69岁。 1.2 纳入与排除标准 1.2.1 非难治性抑郁症病人组 纳入标准: 符合CCM D-3抑郁发作诊断标准,未经抗抑郁药物治疗或曾经使用过一种抗抑郁药治疗有效,目前仍符合抑郁发作诊断标准; 汉密尔顿抑郁量表17项评分≥18分; 自愿签署知情同意书。排除标准: 合并严重躯体疾病的患者; 既往有过躁狂发作者; 入组前一月内接受过非选择性单胺氧化酶抑制剂(M A O I)治疗的患者; 入组前2个月内接受过长效神经阻滞剂治疗的患者; 入组前2个月内接受过甲状腺素治疗的 患者及家属因病耻感所带来的负性影响。 4 参考文献 [1]徐晖,李峥.精神病患者病耻感的研究进展[J].中华护理杂志, 2007,42(5):455-457 [2]W ahl O F.M ental health consum ers'exper ience of stigma[J]. Schizophr enia b ullet,1999,25(3):467-478 [3]L ink B G,Yang L H,Phelan J C,et al.M eas uring mental illness s tigma[J].S chiz ophren ia Bulletin,2004,30(3):511-541 [4]陈熠,岳英,宋立升.精神病患者家属病耻感调查及相关因素分析 [J].上海精神医学,2000,12(3):153-156 [5]潘效明,宋立升.重性精神病患者及家属病耻感调查和相关因素研 究[J].中国民康医学,2010,22(15):1961-1962 [6]Angermeyer M C,M ats chinger H.Th e stigm a of mental illnes s: effects of labeling on public attitudes tow ards people w ith mental dis or der[J].Acta Psychiatrica Scandin avica,2003,108(4):304-309 [7]M ichael R,Ph lillips,Veronica,et al.Stigma and express ed emotion:a study of people w ith s chizoph renia and their family m emb ers in China[J].Th e British J ou emal of Ps ych iatry,2002, 181:488-493 (收稿时间:2011-02-18) 中国.四川内江市第一人民医院 641000 E-m ail:las0731@https://www.doczj.com/doc/c715360333.html,
1.心理咨询的工作范围 2.判断正常与异常的心理活动三原则： 1）主客观世界的统一性（有自知力/无自知力） 2）精神活动的内在协调一致性（心理过程（知、情、意）之间具有协调一致）3）个性的相对稳定性（没有外部原因，人格的稳定性出了问题） 3.一般心理问题 原因：由现实因素而产生，内心冲突，体验到不良情绪（如厌烦、后悔、懊丧、自责等）。 时间：不间断持续满一个月，间断持续两个月。 程度： 1）可控：不良情绪反应仍在相当程度的理智控制下，始终能保持行为不失常。2）社会功能：基本维持正常生活、学习、社会交往和工作，但是效率有所下降。3）未泛化：不良情绪的激发因素仅仅局限于最初事件，即便是与最初事件有联系的其他事件，也不引起此类不良情绪。 4.严重心理问题 原因：较为强烈的、对个体威胁较大的现实刺激。体验着痛苦情绪。 时间：间断或者不间断持续时间在两个月以上，半年以下。 程度： 1）不可控：多数情况下，会短暂的失去理性控制；单纯地依靠自然发展或非专业性的干预，却难以解脱。 2）社会功能：对生活、工作、社会交往都有一定程度的影响。 3）泛化：痛苦情绪不但能被最初的刺激引起，而且与最初刺激相类似、相关联的
刺激，也可以引起此类痛苦。 5.神经症：神经症是一种精神障碍，主要表现为持久的心理冲突，病人觉察或体验到这种冲突并因之而深感痛苦，且妨碍了心理功能或社会功能，但没有任何可证实的器质性病理基础。 特点： 1）有自制力 2）精神痛苦 3）持久性 4）妨碍社会功能 5）没有任何器质性病变作为基础 6.神经症的临床分型 恐惧症焦虑症抑郁症强迫症神经衰弱躯体形式障碍 7.神经症的诊断标准 1）症状标准：恐怖症状、焦虑症状、强迫症状、惊恐发作、神经衰弱症状 2）严重标准：主观上无法摆脱的精神、情绪、内心痛苦；客观上社会功能受损，无法正常生活、学习和工作 3）病程标准：符合症状标准至少3个月，惊恐障碍1个月 4）排除标准：排除器质性精神障碍、精神活性物质障碍、严重精神障碍心理问题比较 8.