Pharmacotherapy for the Treatment of Hoarding Disorder

Hoarding disorder, which is characterized by difficulty discarding or parting with possessions, is common and potentially “disabling.” In fact, this behavior usually has some harmful effects, such as emotional, physical, social, financial, and even legal implications. Also, people who hoard often exhibit irrational behavior.

In some studies, hoarding has been listed as diagnostic criteria for obsessive-compulsive personality disorder (OCPD); however, some consider hoarding a disorder in itself. There are various routes of treatment for hoarding disorder, including both psychotherapy and pharmacotherapy. For the purpose of this assignment, I will focus more on the pharmacotherapy.

Since hoarding disorder is closely associated with OCD, pharmacotherapy for the treatment of hoarding disorder is similar to treatment of OCD. Studies have shown that OCD patients respond well to the use of selective serotonin reuptake inhibtors (SSRI’s), and some of these drugs have clinical effect in patients with hoarding behavior/disorder. In one study done by Sanjaya Saxena, it was concluded that the use of paroxetine (Paxil), which is an SSRI, improved hoarding symptoms, depression, and anxiety. Furthermore, venlafaxine has also shown good response with hoarding behaviors. In fact, venlafaxine had a trend for greater reduction in hoarding symptoms than that seen with paroxetine. New treatment strategies might also include cognitive enhancers, such as donepezil, to increase attention and executive functioning in patients with hoarding disorder.

In conclusion, hoarding disorder is a common and relevant problem that can tremendously affect someone’s life, but can be treated. Hoarding disorder, along with its signs and symptoms, can be improved by pharmacologic therapy (mostly the use of SSRI’s), psychological therapy, or a combination of both.

 

http://www.uspharmacist.com/content/d/pharmacy_focus/c/58008/

Saljoughian, Manouchehr. Hoarding Disorder: Diagnosis and Treatment. US Pharm. 2015:40(11):60-62.

From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets

This paper touches on the complexity of post-traumatic stress disorder and the challenges associated with finding new treatment for patients with the condition. Like other anxiety disorder, PTSD is often treated with selective serotonin reuptake-inhibiting medications, and has been for decades. Psychological therapies are time-consuming and laborious, while pharmacological treatment with SSRIs suffers from lack of effect, relapse, and side effects. On top of that, both type of treatments seem to work only in a subset of patients. More effective treatment with fewer side effects is needed.

One large obstacle to pharmacological and non-pharmacological treatment of this disease is the establishment of an animal model. The large number of PTSD symptoms and the strong cognitive component in this anxiety disorder make it difficult to find a valid animal model for PTSD that meets all the criteria. There exists three animal models for PTSD currently: early life stress, inescapable foot shock (IFS), and social defeat. No model is perfect though the IFS model does provide a reproducible traumatic event, allowing researchers to manipulate the severity of the trauma for experimental reasons. While the early life stress and social defeat models may provide a benefit for the research on sensitivity to trauma, the IFS model is generally regarded as the best. However, symptoms that are not likely to be modeled in animals, such as flashbacks, intrusive memories, and nightmares, will still remain.

In an effort to reduce anxiety from PTSD via non-pharmacological means, two therapies have been identified: environmental enrichment combined with voluntary exercise and methods for re-exposure to the fear-eliciting stimulus in order to initiate extinction. Environmental enrichment enhances neurogenesis in the dentate gyrus and stimulates dendritic branching and spine forming in the hippocampus, effects also often seen after treatment with anti-depressants. By understanding the mechanisms underlying the beneficial behavioral changes of environmental enrichment, we may be able to elucidate future pharmacological treatment possibilities.

Re-exposure treatment is also an effective non-pharmacological psychological therapy option because exposure to a fearful stimulus in a safe environment can decrease the emotional reaction that this stimulus elicits in future exposures. This treatment involves an associative learning process known as ‘extinction’. MRI scans have shown that the areas involved in extinction, amygdala, hippocampus, and prefrontal cortex, are affected in PTSD patients. It is likely that re-exposure induces many other changes in gene expression. The challenge is how to identify those molecular changes that are causally related to the beneficial effects of this non-pharmacological treatment.

From the animal models discussed in the paper, the IFS model shows the most potential for patients with PTSD though it still is not perfect. Animal models help to acquire knowledge of the mechanisms underlying non-pharmacological interventions that can point out neurobiologically relevant processes leading to behavioral recovery. If we understand why the behavioral therapies are good for the brain, we may be able to identify new therapeutic targets.

Hendrikus Hendriksen, Berend Olivier, Ronald S. Oosting, From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets, Eur J Pharmacol. 2014;732:139-158

Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports

The focus of this study was to reanalyze previous studies using Bayesian analysis to determine which SSRIs, if any, were associated with different types of birth defects.

The study took place across 10 centers in the U.S., with almost 18,000 mothers of infants who did not experience birth defects and almost 10,000 mothers of infants who did experience birth defects. The study then looked to see if these mothers had used citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before pregnancy through the third month of pregnancy. The study was adjusted to take into accound race/ethnicity, education level, smoking, and obesity of the mother.

The study concluded that the most commonly used SSRI was sertraline, but no birth defects could be correlated to the use of this drug. There were also no defects strongly correlated with citalopram or escitalopram. The researchers concluded that some birth defects did occur 2-3.5 times more frequently in the infants of women using paroxetine or fluoxetine early in pregnancy.

This study is interesting to me, as it gives us a better guideline of which SSRIs are safer to use in pregnant women. If the switch from one type of SSRI can dramatically reduce the risk of birth defect, I think most mothers would be happy to know this and would be very likely to switch medications.

Link to Article

Polymorphism Associated with the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depression

Are pharmacogenetics-based strategies the key to effective depression treatment? This study set out to dig deeper into this questions by researching additional polymorphisms affecting the efficacy of SSRIs. Previously, a polymorphism in the serotonin transporter linked promoter region was found to be associated with a difference in SSRI efficacy. This polymorphism, however, only explained a small amount of the differences in efficacy seen in the treatment of those with depression. So this study intended to find additional polymorphisms in the gene coding for the serotonin transporter (SLC6A4) accounting for different responses in SSRI/SNRI treatment. (Remember that the serotonin transporter is the target of serotonin uptake inhibitors)

A 6-week randomized controlled trial of 201 patients with major depressive disorder was performed. Subjects were given paroxetine 20-40 mg/d (SSRI), fluvoxamine 50-150 mg/d (SSRI), or milnacipran 50-75 mg/d (SNRI). Efficacy of the therapy was measured by comparing baseline Hamilton Depression Rating Scale (HAM-D) values with those from the end of the 6 week treatment period. Genomic DNA was gathered from each patient and sequenced so that SLC6A4 mutations could be analyzed. 32 variants were found, and 17 of these were new polymorphisms. One of the polymorphisms, rs3813034, resulted in significantly altered HAM-D scores for each medication administered, suggesting it has an effect on SSRI/SNRI response.

Considering all the treatment hurdles those with depression face (medications take a lot of time for effects to be realized and they may not be effective for many people), I think it is important to research the pharmacogenetics involved with SSRIs. This can help create more individualized treatments for patients who do not have months to spend time putting their well-being on hold while they try numerous antidepressants before finding one that works. Do you think it would be practical and possible to someday have a genotype-based protocol for antidepressant treatments?

Nonen, S et al. Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4. J. Clin. Psychopharmacol. 2016; 36(1):27-3.

SSRIs May Increase the Risk of Violent Behavior in Young People

Selective serotonin reuptake inhibitors, or SSRIs, are among the most commonly prescribed antidepressants. These drugs are not generally used in adolescents and young adults as several studies have suggested that SSRIs increase the risk of suicidal ideation in these age groups, but not in adults. SSRIs are also believed by some to cause violent behavior, particularly in adolescents and young adults, although the data on this is much more inconclusive. Therefore, one group of researchers in Sweden designed a study to try and determine a possible correlation between SSRI use and violence in adolescents. The researchers used records available from the Swedish Prescribed Drug Register to identify 856,493 patients over the age of 15 who had been prescribed SSRIs in the period between January 1, 2006 and December 31, 2009. The researchers then examined the arrest records of these patients and compared individual patient records when they were on SSRI treatment to when they were not on an SSRI treatment.

Of the entire patient population studied, 9.9% were between the ages of 15 and 24, and these individuals were considered adolescents or young adults. Upon examining the arrest and conviction records of this population, it was determined that this group was more likely to be convicted of a violent crime while on SSRI treatment, although only low doses of SSRIs produced this result. Patients in this age group on moderate or high doses of SSRIs and patients in other age groups on any dose of SSRI did not show a significant increase in violent crime. Within the 15 to 24 age group, the use of medications that could serve as an alternative to SSRIs, such as venlafaxine, was also associated with an increase in violent crime. The study could not determine the cause of this association, and recommended that further studies should be conducted to corroborate their findings.

Given their potential to increase suicidal ideation and possibly the rate of violent crime among adolescents and young adults, is there any case for using SSRIs in adolescents? Would giving a young person large doses of an SSRI really be the most effective treatment option?  With this study’s suggestion that other antidepressant treatments may also increase violent behavior in adolescents, is it possible that antidepressant medication as a whole may not be appropriate for adolescents or young adults?

 

 

Molero Y, Lichtenstein P, Zetterqvist J. Selective serotonin reuptake inhibitors and violent crime: a cohort study. PLoS Med. DOI: 10.1371/journal.pmed.1001875 (published 15 September 2015)

Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding

Selective serotonin receptor inhibitors (SSRIs) are usually used as the first line medications to treat depression and other psychogenic disorders. The main concerns of using SSRIs is the increased risk of internal bleeding including gastrointestinal, genitourinary, and intracranial bleeding. This article is about the nationwide study that was done in Taiwan to discover whether SSRI or serotonin- noradrenaline reuptake inhibitors (SNRIs) usage causes increased risk of internal bleeding.

The subjects were randomly picked from Taiwan National Health Insurance Research Database.  The study group consists of 8809 SSRI users and 944 SNRI users. Patients with alcohol related disease, inflammatory bowel disease, bleeding of GI tract before January 1, 2000 were excluded from the study. The control group consists of 39,012 subjects who had not taken SSRI or SNRI. Both groups were followed from 2000 to 2010.

The results showed that the SSRI group users had a much higher incidence of upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding (LGIB) than the control group. The results also showed that SSRI are more likely to cause LGIB than UGIB. The possible reason behind this is that SSRI decreases serotonin availability which is an important factor in platelet aggregation. SSRIs also increases gastric acid secretion and aggravation of NSAID-induced gastric mucosal injury. The study also noticed that male are more likely to experience UGIB and LGIB than female.

This study is very interesting to me. SSRIs and SNRIs are relatively new classes of medications so this study shows that researchers are still trying to find out possible side effects of these medications. Now that there is strong evidence that there is a strong link between SSRIs and GI bleeding, I am interested in whether SSRIs will still continue to be the first line medications used to treat depression and other psychogenic disorders. I am also interested in other differences between SSRIs and SNRIs.

Citation:

Cheng Yuan-Lung, Hu Hsiao-Yun, Lin Xi-Hsuan, Luo Jiing-Chyuan, Peng Yen-Ling, Hou Ming-Chih, Lin Han0chien,Lee Fa-Yauh. Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding: A Nationwide Population-Based Cohort Study in Taiwan. Medicine.10.1097/MD.0000000000002022. (published 20 November 2015).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652818/