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Issue 79, Nov 2018
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Antidepressant-induced mania in bipolar disorder. Who is at risk?

Williams AJ et al. J Clin Psychiatry. 2018 May/June; 79(3). Pii 17m11765.doi: 10.4088/JCP.17m11765 PMID: 29873955

Background

There is ongoing use of antidepressant medications in bipolar disorder for treating depressive symptoms, despite the cloud of antidepressant induced mania (AIM). Multiple studies suggest that antidepressants have limited if any role in treating this illness. This study has sought to help the clinician by exploring socioeconomic, demographic, and clinical factors that help predict risk of developing mania in bipolar patients treated with antidepressants.

Methods

This clinical retrospective study conducted between February 2006 and December 2010 included patients in the bipolar spectrum (bipolar I, bipolar II, bipolar NOS, and schizoaffective disorder bipolar type).  Diagnosis was made using DSM-IV criteria. Statistical methods were used to ascertain which factors contributed to antidepressant exposure as well as the clinical factors resulting in AIM in bipolar patients.

Results

The results suggest that factors including female sex, older age, chronicity of illness, and white race had a greater likelihood of antidepressant exposure. Greater number of prior manic episodes and affective psychosis resulted in lower antidepressant exposure. Female sex was the only factor statistically significant in reporting AIM.

Conclusions

This study suggests that female sex, older age, chronicity of illness, and white race are associated with antidepressant exposure in bipolar depression. Female sex is both a risk factor for antidepressant exposure as well as a risk factor for AIM.

Clinical Commentary

There is an ongoing controversy regarding the use of antidepressants for bipolar illness. Antidepressants are prescribed for these patients 2:1 compared with mood stabilizer therapy, despite the FDA and treatment guidelines. This is the first study suggesting that female sex is clearly a risk factor for antidepressant prescription as well as AIM.  In this difficult to treat population we should not use antidepressants without a mood stabilizer, be extremely careful in female patients with chronic illness and try to establish an accurate diagnosis.  The mood disorder questionnaire as well as collateral information, in addition to a thorough interview using longitudinal assessment are essential in making an accurate diagnosis. Patients with failure of multiple antidepressant trials, family history of bipolar illness, and postpartum depression are likely to have receive antidepressant therapy as the bipolar disorder diagnosis may be missed. These factors are red flags for a bipolar disorder diagnosis in a patient presenting predominantly with depressive symptoms.

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Does excessive internet usage cause suicidal thoughts and behaviors?

Cheng YS et al. J Clin Psychiatry. 2018 June 5;79(4). Pii17r11761. doi:10.4088/JCP. 17r1111761. PMID:29877640

Background

Internet addiction has become a commonly discussed topic in today’s society due to easy access to email, social media, video games, online shopping, and online banking via a handheld device such as a smartphone or tablet. This addiction is affecting teenagers and other young people in multiple ways. Internet addiction disorder is not a formal diagnosis in the DSM-5, and the question exists whether this addiction is a result of an underlying psychiatric disorder, such as depression, or if it is an independent issue. Multiple studies from Europe and Asia have analyzed the association between internet addiction and suicidality to determine if mental illness is a primary contributing factor to suicidal thoughts and behaviors seen in addicted internet users. The study seeks to investigate the relationship of internet addiction and suicidal ideation/behaviors. It also assessed if there were any differences in those addicted to the internet and those with internet gaming problems.

Methods

This meta-analysis included observational (cross-sectional, case control, prospective studies) and 2 prospective studies investigating the relationship between internet addiction and suicidality. A thorough search of electronic databases such as PubMed, Embase, Clinical Key, Cochrane Library, ProQuest, Science Direct, and Clinical Trials.gov was conducted (N=1,180). To assess if an individual had internet addiction, criteria such as preoccupation, negative mood management, tolerance, withdrawal, external conflicts, and lack of control were considered in addition to usage of Young’s Internet Addiction Test, Chen Internet Addiction Scale, and Korea Internet addiction scale. The rates of suicidal ideation, planning, and attempts in individuals with internet addiction and controls was investigated.

Results

The prevalence of internet addiction and gaming disorder varied from 0.6% to 22.8% across studies.

  • The severity of suicidal ideation was significantly higher in participants with internet addiction compared to controls.
  • After adjusting for demographics and depression, the odds of suicidal ideation/attempts was1.5 times higher in those with internet addiction.
  • Children under 18 years had a significantly higher prevalence of suicidal ideation than adults.
  •  Individuals with internet gaming disorder had higher rates of suicidal thoughts and behaviors compared to non-gamers.
Conclusions

This study provides evidence that internet addiction increases the rates at which individuals, primarily adolescents, have suicidal thoughts and behaviors, regardless of underlying depression or other confounding variables. The effect may be that of the websites used for surfing, as well as impulsivity from gaming. Gamers have a higher risk that non-gamers who have internet use disorder. DSM criteria are not specifically defined (conditions for further study) for internet/gaming disorder.

Clinical Commentary

Since adolescents are at the highest risk for developing internet addition, pediatricians and other health care professionals should be screening for internet related problems during routine visits. Screening questions could be

  • The number hours /day spent on internet/gaming
  • Are parents aware of internet sites/games used as the violent games have a greater association with suicidal thoughts/behaviors

This study also suggests that non-depressed gamers as well as those with internet use disorder should be asked specifically about suicidal ideation. Parents should be included in the discussion regarding limiting use of cell phone, computer, and video games usage on a daily basis. These issues are often the cause of sleep problems in these individuals.

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The offspring of patients with major psychiatric disorders: What are the risks?

Rasic D et al. Schizophr Bull. 2014 Jan; 40(1):28-38. doi: 10.1093/schizbull/sbt114. E pub 2013 Aug 19. PMID: 23960245

Background

The field is aware about the increased risk of severe mental illness (SMI) such as schizophrenia, bipolar disorder, and major depression in the children of those with these disorders. Previous studies have mostly focused on the risk of developing the same disorder as the parent in the offspring.  Before this study was conducted, previous research demonstrated a 1 in 10 chance that a child born to a parent with SMI would also develop SMI. The article demonstrates that the answer to the question “if I have SMI, what are the chances my child will have SMI?” has drastically changed.

Methods

This study included data from published cross-sectional and longitudinal studies of biological offspring of parents with SMI. The search included major databases such as MEDLINE/PubMed, Embase, and PsycINFO. This study included psychotic disorders as well as the major mood disorders (schizophrenia spectrum disorders, psychotic disorders NOS, bipolar disorder, and major depressive disorder). The offspring were grouped by parental diagnosis and compared to a control group. The offspring were evaluated at a mean age 10 or higher.

Results

 33 studies were reviewed and information was extracted on 3863 offspring of parents with SMI (high risk offspring). There was a 32% probability of developing SMI in offspring of those with SMI by adulthood (age >20). It was more than twice the risk in the control offspring.

  • High risk offspring has a significantly higher risk of developing the same illness as the parent (3.5 times higher).
  • The risk of developing an SMI not present in the parent was significantly higher too (1.9 times more likely).
  • There was a significantly elevated risk of mood disorders in offspring of patients with schizophrenia.
  • The risk of schizophrenia was higher in offspring of parents with bipolar disorder.
Conclusions

This study demonstrates that by early adulthood, 1 in 3 children born to a parent with SMI will also suffer from schizophrenia, bipolar disorder or major depressive disorder. Furthermore, these children have a 1 in 2 chance that they will develop any mental disorder, such as generalized anxiety disorder, OCD or eating disorders.

Clinical Commentary

The familial risk of SMI extends beyond diagnostic boundaries which is important clinically. We as clinicians need to inform patients regarding these risks as part of their treatment perhaps not at the first visit but in ongoing treatment once the patient is stable and able to process such information. The patients will be empowered with important information for decision making regarding having children as well as being watchful about symptoms in their offspring so screening as well as early intervention can be done. We as clinicians know that early and accurate treatment of SMI has better outcomes.

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Antidepressant combination versus antidepressant and second-generation antipsychotic augmentation for treatment-resistant unipolar depression: Which one to choose and when?

Gobbi G et al.  Int Clin Psychopharmacol. 2018 Jan; 33;(1):34-43. doi: 10.1097/YIC. 196. CD003382. Pub3 PMID 28906325

Background

Less than 50 percent of depressed patients remit with the first antidepressant prescribed. Treatment resistant depression (TRD) is a difficult to treat illness.  Psychiatrists often use the combination of two antidepressants (Ads) or the augmentation of antidepressant with a second-generation antipsychotic (SGA) to treat TRD.

Methods

This study included data from N=106 patients aged 19-80 years.  The diagnosis of participants was verified using the Structured Clinical Interview for Diagnosis (SCID). All patients selected had unipolar depression without manic/hypomanic symptoms. Finally, N=86 participants were included who received ADs or a combination of SGA+AD. The patients had tried at least two antidepressants before getting to this level of treatment. The Ads combination group included N=36 and the group-SGA+AD included N=50 participants. Depression rating scales were used to evaluate the symptoms.

Results

The participants had a diagnosis of major depression recurrent moderate to severe intensity based on DSM-V criteria. 78% had unipolar TRD without psychotic features and 65% were diagnosed with comorbid anxiety disorders. The TRD patients in the SGA+AD group showed a significantly higher reduction in depression compared to TRD patients in the ADs group. The SGA+AD combination was more effective for severe depression. The ADs and SGA+AD group differed by number of failed pharmacotherapies, presence of psychotic features, personality disorders, history of substance use disorder (SUD), more than one hospitalization since first depressive episode, and levels of depression measured at baseline.

TRD patients with psychotic features were 26 times more likely to receive SGA augmentation. TRD patients with personality disorders were three times more likely to get SGA augmentation, and TRD patients with SUD were five times more likely to get SGA. The study also found that for every failed ADs combination therapy the likelihood of getting SGA augmentation was increased by 34%

Conclusions

This study highlights the importance of considering the SGA augmentation as first-line in severe TRD patients, specifically those presenting with psychotic features, personality disorders, and SUD.

Clinical Commentary

This is the first study of its kind examining outcomes of TRD patients in the real-world setting comparing ADs combination with SGA+AD augmentation. This gives clinicians direction as to when to choose SGA augmentation of an antidepressant versus adding another antidepressant. The sicker patient or those with complications like substance abuse, personality disorders, or psychotic features are clearly those in whom to use the SGA+AD approach. Going this route earlier would cut down treatment time, reduce suffering and improve functioning sooner. The risk of tardive dyskinesia in those with mood disorders receiving antipsychotic therapies needs to be added into the equation.

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Depression as a predictor of the risk of Alzheimer dementia in older adults: What does research reveal?

Gallagher D et al. Am J Geriatr Psychiatry. 2018 Aug;26(8): 819-827.doi: 10.1016/j.ajp.2018.05.002  E pub 2018 May 9 PMID:29960668

Background

There is ongoing interest about the ability to clinically predict risk of Alzheimer dementia (AD).

These risks are not completely understood. Clinicians will be assisted significantly if high risk sub-groups could be identified. This study looked at depression as a risk factor for developing AD in older adults.

Methods

This study reviewed data from the National Alzheimer’s Coordinating Center involving 1965 participants with depression and mild cognitive impairment (MCI). These individuals were followed until development of AD or lost to follow -up.

Results

The study revealed that 40% of these individuals developed AD over an approximately two year follow up period (27 months). The presence of active depression within the last two years had a high rate of association with developing AD. The presence of active depression had a greater risk of AD than remote history of depression.

Conclusions

Older adults with depression and MCI had a high rate of progression to AD. This is a high-risk group.

Clinical Commentary

Older adults presenting with depression should be screened for cognitive impairment and followed closely. The Mini Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and St Louis Mental Status Examination (SLUMS) are helpful. The SLUMS and MOCA are in the public domain. All are easy to conduct in about 20 minutes. Depression should be aggressively treated in these individuals. In addition, clinicians may consider agents like donepezil and memantine if indicated to delay progression. Clinicians should also consider attending to issues such as driving, living will, and health care proxy in these individuals before it is too late.

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Sanjay Gupta, MD
Clinical Professor of Psychiatry, SUNY Buffalo

GME Research Review is a monthly newsletter edited by Sanjay Gupta, MD, Clinical Professor of Psychiatry, SUNY Buffalo. Dr. Gupta selects, summarizes, and provides a clinical commentary on the latest published research in psychiatry. 

We are always carefully evaluating which research papers to discuss in GME Research Review. Have come across a research paper published in the last 6 months that you thought is clinically relevant? Do you want me to analyze it for you and for the benefit of others? Please email Dr. Gupta the citation at [email protected]

To contact GME, email us at [email protected]


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