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 RESEARCH ARTICLE

Personality disorders in ADHD
Part 2: The effect of symptoms of personality disorder on response to treatment with OROS methylphenidate in adults with ADHD

Reid J. Robison, MD

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Frederick W. Reimherr, MD

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Phillip D. Gale, DO

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Barrie K. Marchant, MS

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Erika D. Williams, MSW

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Poonam Soni, MD

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Corinne Halls, MS

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

Robert E. Strong, DO

Mood Disorders Clinic, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

BACKGROUND: This study explored the relationship between personality disorder (PD) and treatment response in a randomized, double-blind, clinical trial of osmotic release oral system (OROS) methylphenidate (MPH).

METHODS: Forty-seven patients entered a crossover trial using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) to assess outcome. A final personality diagnosis was made using staff consensus and information from the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Three post hoc categories were created: PD-negative (no PD; n = 26), PD-positive (patients with 1 PD; n = 11), and PD-plus (patients with 2 or more PDs; n = 10). Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms was assessed using a mixed-model analysis with treatment and personality categories as fixed variables. Average z scores on the WISPI-IV and items endorsed on SCID-II provided dimensional measures of PD severity.

RESULTS: Different treatment effects were observed for the PD subgroups (P < .001). PD-negative patients improved 40% on OROS MPH vs 7% on placebo, and PD-positive patients improved 66% on OROS MPH vs 9% on placebo. In contrast, PD-plus patients improved 26% on OROS MPH vs 23% on placebo.

CONCLUSION: Most patients experienced significantly reduced ADHD symptoms on OROS MPH; however, patients with 2 or more PDs did not. The 2 alternate measures of PD supported this observation in this small exploratory study.

KEYWORDS: ADHD, adult, personality disorder, outcome

ANNALS OF CLINICAL PSYCHIATRY 2010;22(2):94–102

  INTRODUCTION

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood illness that persists through adolescence and into adulthood in many individuals. Studies have documented that childhood ADHD is associated with an array of other psychiatric disorders, including oppositional defiant disorder (ODD), conduct disorder (CD),1 specific learning disabilities (eg, dyslexia), and various anxiety disorders. In adulthood it is also connected with substance abuse,2 generalized anxiety disorder, obsessive-compulsive disorder, major depression, dysthymia, and bipolar disorder (BD).3,4

A number of studies suggest that ADHD is also connected with adult personality disorder (PD). Studies have reported an increased rate of Axis II disorders in adults with ADHD.5,6 One of the disorders most closely connected to ADHD is CD in adolescence and antisocial disorder in adults.6-11 Family studies suggest that ADHD with CD represent a specific subtype of ADHD, with familial risk factors that are independent of ADHD alone.12 Studies have shown that CD is more severe and persistent in the context of ADHD, and that children with ADHD plus CD are more aggressive and have an earlier age of onset of CD, compared with children with CD alone.13-15 CD in children with ADHD was also found to be a strong predictor of later substance abuse.16

Beyond this, there is a gradually expanding literature connecting ADHD to PDs within cluster B,17,18 a wide range of personality traits,19-21 and other PDs.22-25

Two problems undermine our understanding of these studies and the relationship between PD and ADHD. The first is the fact that the symptoms of ADHD overlap with several PDs.26 This may lead to the overdiagnosis of PDs in adults with ADHD. The second is the limited agreement between physician assessment, self-report scales, and interview approaches.27-32 Consequently, although the above-cited studies are suggestive of a link between ADHD and the presence of PD, there is a need to explore this association more rigorously.

In the first article in this series [see Personality disorders in ADHD. Part 1: Assessment of personality disorder in adult ADHD using data from a clinical trial of OROS methylphenidate.],33 we reported that 45% of the patient sample in this clinical trial had at least 1 PD and 21% had multiple PDs. Most clinicians and researchers would assume that the presence of these PDs would lead to meaningful consequences in terms of psychopathology and/or treatment response. However, there are no reports in the literature exploring these very important questions.

In the third article in this series [see Personality disorders in ADHD. Part 3: Personality disorder, social adjustment and their relation to dimensions of adult ADHD],34 we presented information regarding the interaction of PD with the dimensions of ADHD and social adjustment.

This article assesses the relationship between PD and treatment response in a clinical trial of adults with ADHD.

The presence of PD has been negatively related to outcome of a variety of psychiatric disorders in clinical trials.35,36 A study of nortriptyline in treatment-resistant major depressive disorder found a decreased treatment response (defined as a ≥50% reduction in total 17-item Hamilton Rating Scale for Depression [HAMD-17] score) in patients with avoidant PD.35 A 2003 review by Reich found evidence that Axis II disorders may cause a poorer treatment outcome of an Axis I disorder.37 Little is known about the effect of PD on treatment response in adult ADHD. Because PDs may impact treatment outcomes in other psychiatric disorders, we included measures of PD in a clinical trial of osmotic release oral system (OROS) methylphenidate (MPH) to investigate the effect of PD on treatment in ADHD.

The questions addressed by this study were:

  1. What is the relationship between PD subgroup and treatment response?

  2. Do patients with a limited PD symptom load respond better to ADHD treatment than those with greater symptoms of PD?

  3. Are baseline personality measures (Wisconsin Personality Inventory IV [WISPI-IV] and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders [SCID-II]) able to identify patients who are unlikely to show a treatment effect?

  METHODS

The University of Utah Institutional Review Board reviewed and approved the study. The study was conducted in accordance with the 1975 Declaration of Helsinki. Participants were recruited from the community on an outpatient basis, and following an initial brief screening interview, informed consent was obtained. There was a placebo-controlled trial of OROS MPH that included a screening phase, followed by a double-blind crossover phase with two 4-week arms. The 6-month open-label treatment phase immediately followed the double-blind phase.

Evaluation of PDs was conducted as follows. Patients completed the SCID-II screening questionnaire and SCID-II interviews, which were administered by the same clinician (E.D.W.), who is experienced in both initial evaluations and in the use of programmed interviews. Patients then completed the WISPI-IV questionnaire. The treating psychiatrists recorded their Axis II diagnostic impression using the Iowa Personality Disorder Screen at this time as well as 3 other visits: at the end of each double-blind arm plus the open-label period. The intent of this particular study protocol was to maintain awareness of the patient’s personality characteristics throughout the course of the study. Following the conclusion of the patient’s participation in the study, all available information was reviewed and a consensus decision regarding the patient’s PD was made. This final consensus diagnosis by the clinicians was used as the “gold standard” for the study.

During the double-blind phase, patients were seen on a weekly basis. Medication was started at a dose of 18 mg/d, and the dose was increased every 2 to 3 days by 9 mg, based on patient response and tolerance, up to a maximum dose of 90 mg/d. Treatment response was assessed weekly using the WRAADDS and CGI-I. After a patient was rated as much improved or better on the Clinical Global Impression–Improvement scale (CGI-I), or improved ≥50% on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the dose remained constant for the remainder of that treatment arm. In the event of unacceptable side effects, dose reductions were permitted. Generally, a stable dose was obtained in 2 weeks and then held constant the last 2 weeks.

Study population

Participants were required to meet DSM-IV-TR criteria for current ADHD based on the Conners’ Adult ADHD Diagnostic Interview for DSM-IV, with at least moderate ADHD symptoms. Participants were also required to meet the Utah Criteria for the Diagnosis of ADHD in adults. Participants were between age 18 and 65. The following DSM-IV Axis I diagnoses were exclusionary: current diagnosis of major depressive disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, bipolar disorder, schizophrenia, and other psychotic disorder. Current substance abuse diagnoses were exclusionary.

Measures

The Parent Rating Scale (PRS)38 and the Wender Utah Rating Scale (WURS)38 were used to assist in characterizing the childhood symptoms of the sample. The PRS was completed by the patient’s parents when available. This study measure asks the parent to rate their now-adult child on 12 different symptoms. The WURS relies on the patient’s self-report of their grade-school years. Both have been validated and scores above the 90th percentile on the PRS are associated with positive treatment outcome.

The WRAADDS and the Clinical Global Impression–Severity scale (CGI-S) were used to assess the efficacy of OROS MPH on ADHD symptoms. The WRAADDS is an interviewer-administered scale that assesses the adult ADHD symptoms from the Utah Criteria. In WRAADDS, the scales of attention + disorganization are quite similar to the DSM-IV item of inattention. The scales of hyperactivity/restlessness + impulsivity are similar to the DSM-IV item of hyperactivity/impulsivity. The scales of temper + affective lability + emotional overreactivity have been combined and are called emotional dysregulation, following previous protocols.39,40 Although emotional dysregulation does not contain symptoms recognized in the DSM-IV, there is significant evidence that it is an integral part of ADHD, including the fact that it responds to treatment in parallel with the 2 DSM-IV symptoms.39-41

The ADHD rating scale, which is interviewer administered, assesses the 18 items of the DSM-IV. This scale includes a total score and the subscales of inattention and hyperactivity/impulsivity.

Categorical outcome response was defined by scores of ≤3 on the CGI-S.

The WISPI-IV, a self-administered scale, consists of 214 items derived from the interpersonal perspective of Lorna S. Benjamin,42 with demonstrated validity.43 Patients were categorized as having a PD if they met the test developer’s criteria for a diagnosis consisting of: (a) meeting 100% of DSM “necessary items;” and (b) the percentage of “necessary items” exceeded the percent of “exclusionary items” by at least 50%. Patients were segregated into 3 post hoc categories: PD-negative, PD-positive, and PD-plus.

The SCID-II44 is an interview-based, 2-step assessment system for PD. The patient completes a screening questionnaire and then a follow-up interview is conducted to check on areas that the patient has rated over a threshold level. As with the WISPI-IV, patients were segregated into 3 post hoc categories: PD-negative, PD-positive, PD-plus.

A final diagnostic assessment was completed for each patient at the end of their participation. This was accomplished by the psychiatrist taking into account all data sources (including SCID-II and WISPI-IV). This final psychiatric assessment was used as a “gold standard” for the patients’ personality status. Based on this final diagnosis, patients were again classified into 3 post hoc categories: PD-negative (patients without a PD), PD-positive (patients meeting full diagnostic criteria for only 1 disorder), and PD-plus (patients meeting full diagnostic criteria for 2 or more disorders). Previous studies have separated groups into similar groups based on the extent of PD symptoms.45 Although these 3 categories were created post hoc, they were made without knowledge of treatment outcome. Treatment outcome did not influence the cutpoints chosen.

Data analysis and statistical procedures

Baseline clinical differences between the 3 PD groups were assessed using a one-way analysis of variance (ANOVA) with group category as the primary variable for continuous outcome measures and Pearson chi-square for categorical outcome measures. The efficacy of OROS MPH vs placebo for the 3 PD groups was assessed post hoc using a mixed-model design, with change from baseline in WRAADDS scores as the outcome variable, treatment and personality status as fixed variables, and patient as a random variable. Chi-square was used to assess categorical outcome defined by the CGI-I. All statistics were 2-tailed, with P < .05, and statistical results were not corrected for multiple comparisons.

Alternative PD categories of the WISPI-IV and the SCID-II were identified using ANOVA in a manner that was exploratory. These categories were defined post hoc with knowledge of the patients’ outcomes. All analyses were done using the SPSS 13.0 statistical package.

  RESULTS

Forty-seven patients signed consent for the study. Four patients were eliminated during the baseline phase after meeting criteria for randomization but before entering the first double-blind phase. One patient dropped out during each treatment arm without contributing usable efficacy data. Forty-one patients completed the double-blind trial and are represented in the analysis of treatment effects.

The final diagnostic assessment found that 26 (55%) patients were PD-negative, 11 (23%) patients were PD-positive, and 10 (21%) patients were PD-plus. Almost all PDs were represented. TABLE 1 illustrates that PD was associated with numerous clinical differences at statistically significant levels during the baseline evaluation. Of particular note, the WRAADDS scores for hyperactivity/impulsivity (P = .024) and emotional dysregulation (P < .001) were significantly higher for patients who were found to be PD-positive or PD-plus. On the ADHD rating scale, there were no statistically significant differences in hyperactivity/impulsivity or inattention between patients who were PD-negative, PD-positive, or PD-plus.

As documented in a prior publication40 OROS-MPH was associated with improvements in all measures of ADHD for this clinical sample. In this reanalysis, both PD-negative and PD-positive patients responded positively to treatment, but PD-plus patients did not respond to treatment in any of the ADHD symptoms areas. There were significant interactions between PD status and treatment for the total WRAADDS, attention + disorganization, hyperactivity + impulsivity, and emotional dysregulation. As seen in TABLE 2, compared with the other 2 PD groups, the PD-plus patients consistently improved the most in the placebo arm and the least in the OROS MPH arm. Specifically, the main treatment effect for the total WRAADDS was significant (F[1,74] = 13.67; P < .001), as was the interaction between medication and PD (F[2,74] = 3.76; P = .028). The main treatment effect for attention/disorganization was significant (F[1,74] = 12.86; P = .001), but the interaction between medication and PD only approached significance (F[2,74] = 2.60; P = .081). The main treatment effect for hyperactivity/impulsivity was significant (F[1,74] = 14.60; P < .001), but the interaction between medication and PD only approached significance (F[2,74] = 2.46; P = .092). The main treatment effect for emotional dysregulation was significant (F[1,74] = 10.28; P = .002), as was the interaction between medication and PD (F[2,74] = 4.74; P = .012).

The percentage of patients meeting CGI-S criteria for improvement while on placebo and OROS MPH is seen in the FIGURE. Overall, 56% of patients on OROS MPH and 22% of those on placebo met criteria for treatment response based on a CGI-S of <3. However, this treatment response differed for the 3 PD groups such that 78% of the PD-negative group improved on OROS MPH compared with 11% on placebo (χ2 = 7.56; df = 1; P = .01). Similarly, 33% of the PD-positive group improved on OROS MPH compared with 22% on placebo (χ2 = 5.56; df = 1; P = .025). In contrast, 33% of the PD-plus group improved on OROS MPH and 33% on placebo (χ2 = 2.00; df = 1; P = ns)

Not only did the WISPI-IV and SCID-II identify numerous patients with PD, there was general agreement between the 2 measures on the number of PDs each patient had. The number of PDs identified by the final assessment correlated with the WISPI-IV (P < .001) and the SCID-II (P < .001). However, the WISPI underidentified and the SCID-II overidentified PD. As a result, the criteria used to define the 3 PD groups were not as robust when applied to the WISPI-IV and the SCID-II. However, for both measures, alternative cutpoints were more successful in identifying patients who did not respond to treatment.

For the WISPI-IV, the interaction between treatment and PD group on WRAADDS scores did not achieve significance (F[1,75] = 1.65; P = .20) when we used 2 categories of: (1) no or 1 PD; or (2) 2 or more PDs. The lack of significance may have been caused by low numbers of patients in the PD-plus group (as a result of underdiagnosis of PD by this measure). We found that the first group displayed a treatment effect, whereas the second did not. OROS MPH differed from placebo for the first group of 37 patients (P = .001). In contrast, OROS MPH did not differ from placebo for the second group of 4 patients (P = .88). An alternative measure would be the WISPI-IV normative z scores. When z scores were separated into average scores of ≤0.9 and >0.9 there was a significant treatment by z score effect (F[1,74] = 7.17; P < .009). OROS MPH differed from placebo for the 30 patients with z scores of ≤0.9 (P < .001). OROS MPH did not differ from placebo for the 11 patients with z scores >.9 (P = 1.00).

For the SCID-II, the interaction between treatment and PD group on WRAADDS scores was F(1,75) = 3.60; P = .032 when we used the 2 categories of: (1) none or 1 PD; or (2) 2 or more PDs. The significance was limited by numerous treatment responders in the PD-plus group (caused by the overdiagnosis of PD by this measure). OROS MPH differed from placebo for the 28 patients with none or 1 PD (P < .005). OROS MPH did not differ from placebo for the 13 patients with 2 or more PDs (P = .12).

Similarly, on the SCID-II, the number of items endorsed allowed another way to categorize patients. When the sample was categorized into 2 groups (patients who endorsed ≤59 items vs those who endorsed ≥60 items), there was a non-significant treatment by “items endorsed” effect (F[1,75] = 1.65, P = .21). OROS MPH differed from placebo for the 34 patients with less than 60 items endorsed (P = .001). OROS MPH did not differ from placebo for the 9 patients endorsing 60 or more items in the SCID-II (P = .82).


TABLE 1

Baseline demographic and clinical measures for PD-negative, PD-positive, and PD-plus patients (N = 47)

  PD-negativea n = 26 PD-positiveb n = 11 PD-plusc n = 10  
Mean SD Mean SD Mean SD P value
Age 32.0 12.5 29.2 8.6 28.7 8.5 .667
Male (66%) 16 (34%)   6 (13%)   9 (19%)   .179
Female (34%) 10 (21%)   5 (11%)   1 (2%)    
WURS 48.0 15.8 65.0 10.0 64.8 17.5 F(2,46) = 7.3;
P = .002
Total WRAADDS 21.2 2.8 25.2 1.4 25.4 2.2 <.001
  Attention + disorganizationd 3.7 0.5 3.6 0.3 3.9 0.3 .492
  Hyperactivity + impulsivityd 3.0 0.8 3.6 0.3 3.5 0.6 .024
  Emotional dysregulationd 2.6 0.7 3.6 0.3 3.6 0.5 <.001
ADHD rating scale 34.9 9.2 35.0 6.0 40.8 8.2 .165
  Inattention 20.7 4.6 19.7 3.1 21.9 4.2 .540
  Hyperactivity/impulsivity 14.6 5.7 15.2 5.1 19.1 6.2 .136
CGI-S 4.3 0.5 5.1 0.4 5.4 0.8 <.001
SCID-II - Number of endorsed itemse 34.0 14.9 48.0 70.9 34.9 11.2 <.001
WISPI-IV—Average z scores -0.1 .6 0.5 0.8 1.7 1.2 <.001
ADHD: attention-deficit/hyperactivity disorder; CGI-S: Clinical Global Impressions–Severity of Illness scale (CGI-S); PD: personality disorder; SCID-II: Structured Clinical Interview for DSM-IV Axis II Personality Disorders; WISPI-IV: Wisconsin Personality Inventory IV; WRAADDS: Wender-Reimherr Adult Attention Deficit Disorder Scale; WURS: Wender Utah Rating Scale.
aPD-negative: Patients did not meet criteria for a PD.
bPD-positive: Patients met criteria for 1 PD.
cPD-plus: Patients met criteria for =2 PDs.
dItem averages reported.
eThe total number of items identified as a problem by each patient on the SCID-II.

TABLE 2

Average change in WRAADDS scores (% improvement) after treatment (OROS MPH vs placebo), subdivided by personality disorder status (PD-negative, PD-positive, or PD-plus)

WRAADDS OROS MPH
Mean ± SD
(% improvement)
Placebo
Mean ± SD
(% improvement)
Treatment, P value Treatment by PD group, P value
Total 9.6 ± 9.3 (42%) 3.0 ± 6.8 (13%) <.001d  
  PD-negativea 7.9 ± 8.8 (37%) 2.2 ± 5.9 (10%) .014e .028f
  PD-positiveb 16.8 ± 7.0 (66%) 2.2 ± 7.2 (9%) .001e  
  PD-plusc 6.6 ± 9.5 (26%) 5.9 ± 8.6 (23%) .878e  
Attention/disorganization 3.0 ± 2.8 (40%) 0.9 ± 2.3 (11%) .001d  
  PD-negativea 2.8 ± 2.7 (37%) 0.9 ± 2.3 (12%) .013e .081f
  PD-positiveb 4.3 ± 2.2 (60%) 0.1 ± 2.4 (2%) .002e  
  PD-plusc 2.0 ± 3.2 (26%) 1.6 ± 2.2 (20%) .736e  
Hyperactivity/impulsivity 2.6 ± 2.7 (40%) 0.6 ± 2.0 (10%) <.001d  
  PD-negativea 2.0 ± 2.8 (33%) 0.4 ± 2.0 (7%) .042e .092f
  PD-positiveb 4.8 ± 1.9 (66%) 0.8 ± 1.8 (11%) .001e  
  PD-plusc 1.9 ± 2.1 (28%) 1.0 ± 2.4 (15%) .420e  
Emotional dysregulation 4.0 ± 4.2 (44%) 1.5 ± 3.2 (16%) .002d  
  PD-negativea 3.1 ± 3.8 (39%) 0.7 ± 2.3 (9%) .016e .012ff
  PD-positiveb 7.7 ± 3.2 (70%) 1.3 ± 3.4 (12%) .001e  
  PD-plusc 2.8 ± 4.2 (26%) 3.4 ± 4.3 (32%) .743e  
OROS MPH: osmotic release oral system methylphenidate; PD: personality disorder; WRAADDS: Wender-Reimherr Adult Attention Deficit Disorder Scale.
aPD-negative: Patients did not meet criteria for a PD.
bPD-positive: Patients met criteria for 1 PD.
cPD-plus: Patients met criteria for =2 PDs.
dResults from mixed-model design; this is the main effect for treatment.
ePaired t test comparing change from baseline under the 2 treatment conditions.
fResults from mixed-model design, this is the interaction between treatment and PD group.

FIGURE Percentage of patients meeting CGI-S criteria for improvement (CGI-S ≥3) while on placebo or OROS MPH

CGI-S: Clinical Global Impressions–Severity of Illness scale; OROS MPH: osmotic release oral system methylphenidate; PD: personality disorder.
aTotal: χ2 = 10.00; df = 1; P = .003.
bPD-negative: Patients did not meet criteria for a PD; χ2 = 7.56; df = 1; P = .01.
cPD-positive: Patients met criteria for 1 PD; χ2 = 5.56; df = 1; P = .025.
dPD-plus: Patients met criteria for =2 PDs; χ2 = 2.00; df = 1; P = ns.

  DISCUSSION

As reported in the first article in this series, a large percentage of the ADHD patients were assessed as having a PD in our final personality assessment. This finding suggests that adult PD is a frequent outcome for childhood ADHD. In addition, 21% of the sample qualified for 2 or more PDs (PD-plus). This finding was confirmed with the use of the SCID-II and the WISPI-IV as dimensional measures of personality severity. This additional finding supports our division of this patient population into our 3 categorical groups: PD-negative, PD-positive, and PD-plus.

We were able to detect significant pretreatment differences between these 3 groups. Although the 3 groups did not differ in either measure of attention (the WRAADDS or the ADHD Rating Scale), this may have been due to a ceiling effect, since all 3 groups showed extensive impairment in attention for both measures. As shown in TABLE 1, patients who were PD-negative, PD-positive, and PD-plus were found to be significantly different at baseline on the Total WRAADDS, the WRAADDS hyperactivity-impulsivity dimension, the WRAADDS emotional dysregulation dimension, and the CGI-S. As expected, patients who were PD-positive or PD-plus showed higher scores on these measures than patients without comorbid PD. In this sample the WRAADDS seemed to measure overall severity better than the CGI-S or the ADHD Rating Scale.

This study suggests a potential relationship between PD and the efficacy of OROS MPH on ADHD symptoms. Whereas the PD-negative and PD-positive subsamples both responded favorably to treatment with OROS MPH, the PD-plus group did not. This lack of treatment response was supported both by low OROS-MPH response rates and high placebo response rates. This observation was true for all ADHD symptom subgroups (attention + distractibility, hyperactivity + impulsivity, and emotional dysregulation). Unlike PD-plus patients, those in the PD-positive group did not show a decreased response to OROS MPH.

These data are, to our knowledge, unique, although several other clinical trials have addressed comorbid ODD or CD. For example, a study by Biederman and colleagues (2007) showed that the presence of comorbid ODD did not affect clinical outcomes in children with ADHD treated with atomoxetine.46 Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid patients to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine. These studies addressing childhood ADHD with ODD—which might be considered a precursor of adult PD—did not detect the bimodal treatment response detected in this study.

Other studies have addressed the effect of comorbid PD on treatment in other psychiatric conditions. One study done in the Czech Republic showed that patients with panic disorder and comorbid PD responded less favorably than those with panic disorder alone.47 Conversely, a study of chronic depression and comorbid PD concluded that Axis II PD comorbidity did not appear to diminish response to treatment.48

These data suggest that baseline measures on the WISPI-IV and/or SCID-II might prove useful in identifying patients who are unlikely to benefit from treatment. For both measures, patients with a high load of PD symptoms did poorly in treatment and would have a less favorable prognosis. However, the psychometric properties of the 2 scales were quite different in this sample and, thus, they required very different cutpoints for this purpose. The WISPI-IV underdiagnosed PD relative to the other 2 measures. Therefore, while the 4 patients with 2 or more PDs responded poorly to treatment, many other nonresponders remained in the PD-negative and PD-positive groups. However, there was an alternative measure that was statistically significant: patients with average WISPI-IV z scores of >0.9.

In contrast with the WISPI-IV, the SCID-II overdiagnosed PD in this sample. Many treatment responders were given 2 or more PDs with the SCID-II. A similar alternative categorization proved more useful: patients endorsing 60 or more items in the SCID-II. If these data are replicated, and patients with high PD symptoms truly have lower drug response rates and higher placebo responses, it may be appropriate in future studies to exclude patients with a certain number of PD diagnoses in order to improve the risk/benefit ratio in research and treatment. Further, clear identification of this specific risk factor may furnish the opportunity to explore more useful treatments for this patient group in the future. Just as the Multimodal Treatment Study of Children with ADHD (MTA) trial found that combined medication and behavioral treatment proved superior for ADHD patients experiencing comorbid internalizing symptoms,49 it seems likely that treatments addressing both ADHD symptoms and PD symptoms will be needed for this subset of patients. These results also suggest the need for careful screening and awareness of comorbid PDs in adults with ADHD.

Limitations

This clinical trial was not originally designed to assess the impact of PD on outcome. It was primarily a clinical trial of OROS-MPH to which measures of personality were attached. As a result, it was powered for the clinical trial and perhaps underpowered to fully examine the impact of PD. Furthermore, this study was limited by the fact that the overall number of patients in the sample, particularly in the various PD subgroups, was small.

The decision to divide patients into 3 groups based on degree of PD symptoms was done post hoc rather than being informed by prior statistical analysis or research. However, creation of the groups was not influenced by any knowledge of treatment outcomes. The alternative categories addressing high PD symptom loads using only data from the WISPI-IV or SCID-II were created with full knowledge of treatment outcomes. Thus, they must be treated with caution until verified by other studies.

Most patients were Caucasian, with few minorities recruited, which is perhaps not representative of most populations encountered in clinical practice. Given the exploratory nature of the study, we did not control for multiple comparisons. Assessment of PD is difficult under the best of circumstances, and with ADHD it can be especially challenging. Certain symptoms of ADHD overlap with one or more PDs, making it difficult to ascertain whether a symptom should be attributed to ADHD, to a comorbid PD, or to both. The question often arises as to whether a PD diagnosis is valid in the presence of ADHD and what meaning it conveys. In response to this difficulty, 2 validated personality assessments and clinical judgment were employed.

  CONCLUSION

This ADHD clinical sample included numerous individuals (21%) who met DSM-IV criteria for 2 or more PDs and another 23% who met criteria for a single PD. Almost all PDs were present in this sample, and none of the 3 personality assessments identified a PD specific to ADHD. Patients demonstrating high levels of PD exhibited poor response to treatment with OROS MPH, whereas patients with 1 or no PD responded positively to treatment. Two baseline measures (WISPI-IV and SCID-II) showed promise in identifying patients with higher dimensional measures of PD or multiple PDs, but additional studies with larger samples are needed to validate these findings.

ACKNOWLEDGEMENTS: The authors would like to acknowledge Donald W. Black, MD, Professor of Psychiatry, Department of Psychiatry, University of Iowa, for his careful review of an earlier version of this article.

DISCLOSURES: Mr. Marchant receives grant/research support from Ortho-McNeil Pharmaceuticals. Drs. Reimherr, Williams, Soni, and Strong and Ms. Halls report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

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CORRESPONDENCE: Fred W. Reimherr, MD, Mood Disorders Clinic, Department of Psychiatry, 30 N 1900 E Rm 5R218, University of Utah Health Sciences Center, Salt Lake City, UT 84132 USA E-MAIL: fred.reimherr@hsc.utah.edu