Exploring age of onset as a causal link between major depression and nonmedical use of prescription medications

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Abstract

Background

Nonmedical use of prescription medications (NUPM) has been associated with major depression (MDD), but the specific processes by which they might interact and influence one another are understudied. This investigation attempted to clarify the relationship between MDD and NUPM by examining whether age of MDD onset influenced current and past NUPM and by examining whether age of NUPM onset influenced lifetime or past year MDD.

Methods

These goals were met through use of data from the 2005 to 2007 National Survey on Drug Use and Health. Analyses utilized design-based logistic regression, and current age and order of MDD onset and NUPM initiation were examined in interactions with age of MDD or NUPM onset.

Results

For each year MDD onset was delayed, odds of lifetime, past year, past 30-day NUPM and substance dependence from NUPM were decreased by 2.3%, 2.6%, 1.9% and 2.3%, respectively. Earlier NUPM onset increased odds of past year (3.8%) and lifetime MDD (4.3%) in young adults, and lifetime MDD (2.5%) in 26–34 age group. Current age also interacted with age of MDD onset, with effects on NUPM pronounced in the 65 and older cohort. Order of MDD/NUPM onset generally did not interact with age of MDD onset, but it did interact with age of NUPM onset; the effects of NUPM onset on past year MDD were only significant in those with NUPM first.

Conclusions

These results highlight the need for further investigations of the interactions between depression and NUPM, particularly to evaluate potential causal relationships.

Introduction

While the use of many addictive substances has declined since the early 1990s, nonmedical use of prescription medications (NUPM) rates appeared to increase in the past 20 years (Compton and Volkow, 2006a, SAMHSA, 2010b). NUPM is often defined as the intentional use of an addictive medication, outside of treatment for a legitimate medical condition under a physician's supervision (Compton and Volkow, 2006b) and it often focuses on four classes of medication: opioids, tranquilizers (typically benzodiazepines), stimulants and sedatives.

Currently, NUPM rates follow only those of alcohol, tobacco and marijuana across age groups (SAMHSA, 2010b). Past year initiates of NUPM in 2009 roughly equaled the number of new initiates of marijuana, cocaine and hallucinogens combined (SAMHSA, 2010b), and data indicate that as NUPM has grown, so have rates of NUPM-related treatment utilization, emergency department visits and overdose deaths (Manchikanti and Singh, 2008, SAMHSA, 2009, SAMHSA, 2010a). These data underscore two points: one, NUPM is likely to be a significant public health concern in the coming decades; and two, there is a need to understand NUPM-related processes to maximize interventions aimed at reducing its scope.

While NUPM is understudied (Barrett et al., 2008, Boyd and McCabe, 2008), research indicates that NUPM is associated with psychopathology (e.g., Huang et al., 2006). Given that the medication classes noted above either have primary indications for the treatment of psychiatric symptoms (e.g., tranquilizers treat insomnia) or ameliorate symptoms as a secondary effect, the link between NUPM and psychopathology appears to warrant further study. Major depression (MDD) appears to be a particularly salient correlate of NUPM (Culberson and Ziska, 2008, Goodwin and Hasin, 2002, Wu et al., 2008a), as it is associated with substance use disorder (SUD) symptoms from NUPM in adolescents (Schepis and Krishnan-Sarin, 2008, Wu et al., 2008b), increased odds of NUPM-related SUD in adults (Huang et al., 2006) and a more severe profile of problematic nonmedical opioid use (Wu et al., 2011). Higher levels of depressive symptoms are linked to non-oral administration and more frequent stimulant nonmedical use (Teter et al., 2010). Finally, higher levels of depressive symptoms are seen in a subgroup of nonmedical users that may be at higher risk for other psychopathology and more frequent NUPM (Hall et al., 2010).

Despite these links, few investigations have looked at potential mechanisms by which depressive symptoms and NUPM interact. These interactions are likely to be captured by one of three causal models. In one, NUPM could be initiated to treat symptoms of depression, or to self-medicate (e.g., Khantzian, 1985). To illustrate, medications in the classes noted above produce some degree of euphoria or pleasure, which could combat sadness and anhedonia; furthermore, stimulants would directly combat many depressive symptoms, while sedatives and tranquilizers could help ameliorate insomnia. Opioids may be nonmedically used to treat somatic symptoms that often occur in MDD. Conversely, NUPM could precipitate depressive symptom development through neurobiological alterations (e.g., Brady and Sinha, 2005). Finally, NUPM and depressive symptoms could also be related through a higher-order third factor that separately causes each (e.g., shared genetic and environmental vulnerabilities; Kendler et al., 2003, McGue and Iacono, 2005).

The strong cross-sectional links between MDD and NUPM would indicate that it is important to evaluate these potential causal relationships. Nonetheless, only one published investigation has done so, using cross-sectional data from wave 1 of the National Epidemiological Study on Alcoholism and Related Conditions (NESARC) to examine nonmedical opioid use (Martins et al., 2009). This work found support for both causal models and the higher-order third factor model noted above, with MDD preceding NUPM indicators in some cases, and NUPM preceding MDD in others.

Thus, the aim of this work was to clarify relationships between MDD and NUPM by examining the role of age of MDD onset on current NUPM and the role of age of NUPM initiation on MDD. Earlier age of MDD onset has been linked to a greater likelihood of poor outcomes in adulthood (Klein et al., 1999, van Noorden et al., 2011, Zisook et al., 2007), and it has been posited to be a distinct, more severe form of the disorder (Kaufman et al., 2001). Earlier NUPM onset appears to increase the risk for SUD from NUPM in adults (McCabe et al., 2007). Age of onset of one has not been evaluated as an influence on the other (e.g., age of MDD onset on current NUPM or vice versa). Given the links between MDD and NUPM, age of onset may be an important factor in the course of both MDD and NUPM. Furthermore, the medications typically used nonmedically can have vastly different properties and interact differently with MDD; thus, a final aim of this work is to evaluate the potential relationships noted above separately by medication class.

For age of MDD onset, our hypotheses were as follows: (1) earlier age of MDD onset would significantly increase the odds of lifetime, past year and past 30-day NUPM and of substance dependence or abuse from NUPM; (2) these effects would vary by current age, as NUPM estimates vary significantly by current age (SAMHSA, 2010b); and (3) the effect of age of MDD onset would be stronger in those who had MDD onset prior to NUPM initiation. For age of NUPM onset, our hypotheses were that: (1) earlier age of NUPM onset would significantly increase the odds of past year and current MDD; (2) these effects would vary by age, given the age differences in NUPM referenced above; and (3) the effect of age of NUPM onset would be stronger in those who had NUPM initiation prior to MDD onset.

Section snippets

Methods

The aims of this work will be met through the use of the 2005–2007 versions of the National Survey on Drug Use and Health (NSDUH), a yearly in-home survey of the civilian, non-institutionalized US population conducted by SAMHSA. These versions of the NSUDH were selected to give a large sample while preserving a consistent format for the survey; versions prior to 2005 and after 2007 included a different psychopathology assessment, raising concerns about the consistency of MDD prevalence

Age of MDD onset: hypothesis 1

Across the sample, age of MDD onset was a significant correlate of all NUPM outcomes except for NUPM-related substance abuse. For each year MDD onset was delayed, the odds of lifetime NUPM were decreased by 2.3% (adjusted odds ratio [AOR] = .98, 95% confidence interval [CI] = .97–.98), the odds of past year NUPM were decreased by 2.6% (AOR = .97, 95%CI = .97–.98) and the odds of past 30-day NUPM were decreased by 1.9% (AOR = .98, 95%CI = .97–.99). Finally, odds of NUPM-related dependence were decreased by

Discussion

These results indicate that earlier age of MDD onset increases odds of lifetime, past year, past 30-day NUPM and NUPM-related substance dependence. In all cases, the odds were between 2.6 and 1.9% higher for each year that MDD onset is earlier. These effects appeared generally across medication classes, though opioids and tranquilizers demonstrated more consistent effects. Current age also influenced the relationship between age of MDD onset and NUPM, as relationships strongest in the 65 and

Role of funding source

The development of this manuscript was supported by research grants R01DA024678 and R01DA031160 from the National Institute on Drug Abuse, National Institutes of Health; NIDA had no further role in study design, the collection, analysis or interpretation of data, the writing of the report, or the decision to submit the paper for publication.

Contributors

Ty Schepis was the primary writer of the manuscript and conducted all statistical analyses. Both authors participated equally in study design, interpretation of the results and in editing of the manuscript. Sean Esteban McCabe also advised on choice and implementation of statistical analyses.

Conflict of interest

The authors note no conflicts of interest.

References (37)

  • J. Ventura et al.

    Training and quality assurance with the structured clinical interview for DSM-IV (SCID-I/P)

    Psychiatr. Res.

    (1998)
  • L.T. Wu et al.

    Non-prescribed use of pain relievers among adolescents in the United States

    Drug Alcohol Depend.

    (2008)
  • L.T. Wu et al.

    Prescription pain reliever abuse and dependence among adolescents: a nationally representative study

    J. Am. Acad. Child Adolesc. Psychiatry

    (2008)
  • M.C. Zanarini et al.

    Attainment and maintenance of reliability of axis I and II disorders over the course of a longitudinal study

    Compr. Psychiatry

    (2001)
  • American Psychiatric Association, 2001. Diagnostic and Statistical Manual of Mental Disorders. Text Revision....
  • S.P. Barrett et al.

    What constitutes prescription drug misuse? Problems and pitfalls of current conceptualizations

    Curr. Drug Abuse Rev.

    (2008)
  • C.J. Boyd et al.

    Coming to terms with the nonmedical use of prescription medications

    Subst. Abuse Treat. Prev. Policy

    (2008)
  • K.T. Brady et al.

    Co-occurring mental and substance use disorders: the neurobiological effects of chronic stress

    Am. J. Psychiatry

    (2005)
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