Psychotic-Like Symptoms in Patients With Depression Linked to Poor Treatment Outcomes
Psychotic-Like Symptoms in Patients With Depression Linked to Poor Treatment Outcomes
December 17, 2010 — Irritability and psychotic-like symptoms, such as hearing voices or experiencing paranoia, are common in outpatients with major depressive disorder (MDD) and strongly linked to poor treatment outcomes, according to new findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
"From a clinical perspective, I think this finding has implications in terms of what the clinician needs to pay even closer attention to in terms of evaluating a depressed patient," lead study author Roy Perlis, MD, MSc, director of the Bipolar Clinical Program at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School in Boston, told Medscape Medical News.
However, other symptoms of bipolar spectrum illness, such as a family history of the disorder and manic-like symptoms, were not found to be associated with resistance to antidepressant treatment — going against the common hypothesis that some cases of difficult-to-treat depression are actually unrecognized bipolar disorder.
"We might expect that people with features of depression, such as irritability, might be less likely to respond well to antidepressants. However, that doesn't mean they're not responding well because they actually have bipolar disorder. And that's the sort of jump that people have made in the past," explained Dr. Perlis.
"Then when we looked at combinations of the clinical features sometimes considered to indicate bipolar spectrum disorder, we did not find that they were associated with poorer outcomes. In other words, individual features matter, but this study did not support the predictive validity of bipolar spectrum."
He noted that this does not mean that bipolar spectrum doesn't exist. "But in terms of how useful is it in evaluating a person with MDD, these results would indicated that it is not as useful as some people might argue.
"I would say worry more when you see a depressed patient who is irritable or reports unusual experiences or beliefs."
The study was published online December 6 in Archives of General Psychiatry.
Challenging Problem
"The distinction between MDD and bipolar disorder remains a challenging clinical problem when individuals present with a major depressive episode," the study authors write.
"Review articles and continuing medical education programs frequently assert that unrecognized bipolarity is a substantial contributor to apparent treatment-resistant MDD. However, this hypothesis has rarely been tested directly," they add.
"By design, STAR*D was intended to represent general clinical populations. So it occurred to us that it is very well suited to answer this question: Is there truly this epidemic of unrecognized bipolar in populations of patients being treated for MDD? And if so, what are the consequences?" said Dr. Perlis.
The STAR*D study assessed 4041 patients between the ages of 18 and 75 years diagnosed as having nonpsychotic MDD at 41 clinical sites across the United States (23 psychiatric care settings, 18 primary care settings).
All participants received open treatment with the selective serotonin reuptake inhibitor citalopram followed by up to 3 sequential next-step randomized treatments.
The main outcome measures for the current analysis were "putative bipolar spectrum features, including items on the mania and psychosis subscales of the [self-reported] Psychiatric Diagnosis Screening Questionnaire (PDSQ), examined for association with treatment outcomes."
Results
Results showed that 30% of the patients reported at least 1 symptom on the psychosis scale in the previous 2 weeks and 38.1% reported at least 1 manic-like/hypomanic-like symptom in the previous 6 months on the PDSQ. A total of 16.2% had both manic- and psychotic-like symptoms.
Irritability and psychotic-like symptoms were significantly associated with nonremission across up to 4 treatment trials.
"However, other indicators of bipolar diathesis including recent manic-like symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance," the investigators write.
Brief depression episode duration, which has been suggested in past research to represent a risk marker for bipolarity, was associated with a greater likelihood of remission in this study.
Of the 3166 patients evaluated for bipolar spectrum illness, 27.6% met the criteria for the disorder. No significant relationship was found between latent bipolarity and treatment resistance.
"Considered as a whole, our results cast doubt on the frequent assertion that unrecognized bipolar disorder is widespread in clinical practice and particularly in treatment-resistant MDD," write the study authors.
"Just because someone has a family history of bipolar or other feature does not make a diagnosis of bipolar. It necessitates looking more closely for that diagnosis. But in and of itself it does not substitute for making an evaluation looking for a manic or hypomanic episode," added Dr. Perlis.
Interesting and Provocative
"I thought this study was interesting and provocative, and my own bias is that I intuitively agree with the conclusions," Michael Gitlin, MD, professor of psychiatry at the David Geffen School of Medicine at the University of California–Los Angeles and director of the Adult Division of Psychiatry at the UCLA Mood Disorders Clinic, told Medscape Medical News.
Dr. Gitlin, who was not involved with this study, noted that there were 2 essential issues.
"First, being psychotic probably implies a less good prognosis among a group of depressed patients. That's not controversial or objectionable, as we've seen that before in other studies," he explained.
"The bigger issue reflects the concern and interest around what are called bipolar spectrum disorders — people who have subtle manic and hypomanic symptoms but not a sufficient severity of duration to formally meet the criteria for the patient having bipolar disorder. And there has been lots of controversy in the field about how wide we should cast the net when we look at these spectrum disorders."
He pointed out that many authors feel that many patients have been misdiagnosed as having MDD and really have bipolar disorder, which would have potential treatment implications, whereas other authors have felt that "we've gotten too caught up in taking vague, nonspecific symptoms and shifting diagnosis based on 1 or 2 symptoms that may or not have diagnostic or prognostic value.
"The second conclusion of this paper is that depressed patients with bipolar spectrum features don't really have a different outcome than those without those features, and therefore those features maybe aren't all that relevant in terms of predicting treatment response," said Dr. Gitlin.
"Intuitively, I agree. There have been so much discussion about the topic and so little research, to have a study with a large number of subjects done in a relatively sophisticated way is a real contribution."
On the basis of the study's results, Dr. Gitlin said clinicians should be cautious about overinterpreting bipolar spectrum features in a depressive population and concluding prematurely that patients will not get better from antidepressants, that they will be harmed by antidepressants, or that they really are bipolar and should be treated with a whole different set of medication options. The paper suggests that "this assumption should really be questioned."
The STAR*D study is funded by grants from the National Institutes of Mental Health. The study authors report several financial disclosures, which are listed in the original article. Dr. Gitlin has disclosed no relevant financial relationships.
Arch Gen Psychiatry. Published online December 6, 2010.
December 17, 2010 — Irritability and psychotic-like symptoms, such as hearing voices or experiencing paranoia, are common in outpatients with major depressive disorder (MDD) and strongly linked to poor treatment outcomes, according to new findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
"From a clinical perspective, I think this finding has implications in terms of what the clinician needs to pay even closer attention to in terms of evaluating a depressed patient," lead study author Roy Perlis, MD, MSc, director of the Bipolar Clinical Program at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School in Boston, told Medscape Medical News.
However, other symptoms of bipolar spectrum illness, such as a family history of the disorder and manic-like symptoms, were not found to be associated with resistance to antidepressant treatment — going against the common hypothesis that some cases of difficult-to-treat depression are actually unrecognized bipolar disorder.
"We might expect that people with features of depression, such as irritability, might be less likely to respond well to antidepressants. However, that doesn't mean they're not responding well because they actually have bipolar disorder. And that's the sort of jump that people have made in the past," explained Dr. Perlis.
"Then when we looked at combinations of the clinical features sometimes considered to indicate bipolar spectrum disorder, we did not find that they were associated with poorer outcomes. In other words, individual features matter, but this study did not support the predictive validity of bipolar spectrum."
He noted that this does not mean that bipolar spectrum doesn't exist. "But in terms of how useful is it in evaluating a person with MDD, these results would indicated that it is not as useful as some people might argue.
"I would say worry more when you see a depressed patient who is irritable or reports unusual experiences or beliefs."
The study was published online December 6 in Archives of General Psychiatry.
Challenging Problem
"The distinction between MDD and bipolar disorder remains a challenging clinical problem when individuals present with a major depressive episode," the study authors write.
"Review articles and continuing medical education programs frequently assert that unrecognized bipolarity is a substantial contributor to apparent treatment-resistant MDD. However, this hypothesis has rarely been tested directly," they add.
"By design, STAR*D was intended to represent general clinical populations. So it occurred to us that it is very well suited to answer this question: Is there truly this epidemic of unrecognized bipolar in populations of patients being treated for MDD? And if so, what are the consequences?" said Dr. Perlis.
The STAR*D study assessed 4041 patients between the ages of 18 and 75 years diagnosed as having nonpsychotic MDD at 41 clinical sites across the United States (23 psychiatric care settings, 18 primary care settings).
All participants received open treatment with the selective serotonin reuptake inhibitor citalopram followed by up to 3 sequential next-step randomized treatments.
The main outcome measures for the current analysis were "putative bipolar spectrum features, including items on the mania and psychosis subscales of the [self-reported] Psychiatric Diagnosis Screening Questionnaire (PDSQ), examined for association with treatment outcomes."
Results
Results showed that 30% of the patients reported at least 1 symptom on the psychosis scale in the previous 2 weeks and 38.1% reported at least 1 manic-like/hypomanic-like symptom in the previous 6 months on the PDSQ. A total of 16.2% had both manic- and psychotic-like symptoms.
Irritability and psychotic-like symptoms were significantly associated with nonremission across up to 4 treatment trials.
"However, other indicators of bipolar diathesis including recent manic-like symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance," the investigators write.
Brief depression episode duration, which has been suggested in past research to represent a risk marker for bipolarity, was associated with a greater likelihood of remission in this study.
Of the 3166 patients evaluated for bipolar spectrum illness, 27.6% met the criteria for the disorder. No significant relationship was found between latent bipolarity and treatment resistance.
"Considered as a whole, our results cast doubt on the frequent assertion that unrecognized bipolar disorder is widespread in clinical practice and particularly in treatment-resistant MDD," write the study authors.
"Just because someone has a family history of bipolar or other feature does not make a diagnosis of bipolar. It necessitates looking more closely for that diagnosis. But in and of itself it does not substitute for making an evaluation looking for a manic or hypomanic episode," added Dr. Perlis.
Interesting and Provocative
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| Dr. Michael Gitlin |
"I thought this study was interesting and provocative, and my own bias is that I intuitively agree with the conclusions," Michael Gitlin, MD, professor of psychiatry at the David Geffen School of Medicine at the University of California–Los Angeles and director of the Adult Division of Psychiatry at the UCLA Mood Disorders Clinic, told Medscape Medical News.
Dr. Gitlin, who was not involved with this study, noted that there were 2 essential issues.
"First, being psychotic probably implies a less good prognosis among a group of depressed patients. That's not controversial or objectionable, as we've seen that before in other studies," he explained.
"The bigger issue reflects the concern and interest around what are called bipolar spectrum disorders — people who have subtle manic and hypomanic symptoms but not a sufficient severity of duration to formally meet the criteria for the patient having bipolar disorder. And there has been lots of controversy in the field about how wide we should cast the net when we look at these spectrum disorders."
He pointed out that many authors feel that many patients have been misdiagnosed as having MDD and really have bipolar disorder, which would have potential treatment implications, whereas other authors have felt that "we've gotten too caught up in taking vague, nonspecific symptoms and shifting diagnosis based on 1 or 2 symptoms that may or not have diagnostic or prognostic value.
"The second conclusion of this paper is that depressed patients with bipolar spectrum features don't really have a different outcome than those without those features, and therefore those features maybe aren't all that relevant in terms of predicting treatment response," said Dr. Gitlin.
"Intuitively, I agree. There have been so much discussion about the topic and so little research, to have a study with a large number of subjects done in a relatively sophisticated way is a real contribution."
On the basis of the study's results, Dr. Gitlin said clinicians should be cautious about overinterpreting bipolar spectrum features in a depressive population and concluding prematurely that patients will not get better from antidepressants, that they will be harmed by antidepressants, or that they really are bipolar and should be treated with a whole different set of medication options. The paper suggests that "this assumption should really be questioned."
The STAR*D study is funded by grants from the National Institutes of Mental Health. The study authors report several financial disclosures, which are listed in the original article. Dr. Gitlin has disclosed no relevant financial relationships.
Arch Gen Psychiatry. Published online December 6, 2010.
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