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September 29, 2020

The Pharma Loaded U.S. Soldier, Part 2: The Footprints Behind the Military Suicide Epidemic, and The Way Forward

In Part 1 of this series, we explored data related to the apparent risks associated with the suicide rate of military personnel with the realization that it’s not only trauma from combat that contributes to risk, but also the pharmaceutical load on soldiers and specific problematic medications. What is the total load on America’s soldiers? U.S. military members are routinely taking up to 19 prescription medications to enhance performance and reduce stress.The collateral damage is that 20 veterans die by suicide every day in the US, when including current active duty, reserve members, and the National Guard. View the full research report with citations, charts and more detailed information. Part 2 will further examine potential causal pharmaceutical-related factors for military suicides and highlight the non-pharma alternatives proving to mitigate risks.

In 2010, the U.S. Army announced its hypothesis on the epidemic of suicides as due to the frenetic pace of Army life:

At first glance, there seemed to be a simple explanation for the increase in suicides: Soldiers were returning from a prolonged, violent war traumatized by their experiences, and some of them took their own lives. While logical, this explanation turned out to be oversimplified. When the Army’s Health Promotion, Risk Reduction and Suicide Prevention Task Force studied cases of suicide, it found that most soldiers who had taken their own lives had deployed only once to Iraq, or not at all, and that deployment-related mental-health troubles didn’t necessarily correlate with suicides. Instead, the committee found that the pace of Army life, particularly during wartime, produced a hectic stream of trainings, deployments, job changes and relocations that placed soldiers under more stress than their civilian peers but that soldiers most often took their lives for the same reasons that civilians did: failed relationships; careers imperiled by legal trouble or injury; mounting debts; or unmanageable depression, anxiety or substance abuse.

While Army pace of life may be a contributing factor to suicides in active duty members, it cannot explain the unacceptably high rate of suicides among veterans. It is also neglectful to mention substance abuse as a factor in military suicides without analysis of the number of prescription medications that veterans consume on a daily basis for long term effect. Military personnel are routinely prescribed numerous medications with Black Box warnings for suicidal thoughts, mania, psychosis, violent behavior, delusions, hallucinations, and psychotic behaviors. Many of these drugs are addictive and prescribed without a plan to wean off dependency. Instead, the needed therapeutic dose will increase over time, along with side effects and risks.

New soldiers anecdotally report being prescribed medications for the expected stress of Basic Training, which will begin the cascading prescriptions for deployment induced trauma and pain from injuries, and will accumulate with additional prescriptions as veterans, for deteriorating physical health associated with unresolved PTSD symptoms (more in Part 1).

The Problem with Antidepressants & Sleep Meds

Some anti-depressants, commonly prescribed to military, as reviewed in Part 1, have not proven better than placebos in veterans with PTSD (see full report for citations):

No difference was found between placebo (n = 26) and fluoxetine (n = 26) in veterans with PTSD (van der Kolk et al., 2007) and placebo (n = 83) and sertaline (n = 86) in veterans with PTSD (Friedman, Marmar, Baker, Sikes, & Farfel, 2007).

Venlafaxine and other anti-depressants can increase the risk of suicide in adolescents. This has dire implications for young military members:

…use of the serotonin–norepinephrine reuptake inhibitor, venlafaxine, with benzodiazepines in SSRI resistant depression in adolescents (n = 334) was associated with a higher rate of suicide and suicide attempts (Brent et al., 2009).

In 2004, the FDA published two public health advisories warning the public that SSRI medications doubled the risk of suicide for both children and young adults ages

18-24, and yet the 2006 Pentagon medication guidelines for depressive disorders allowed widespread prescriptions of SSRI medications that may be contributing to the highest rate of suicide among veterans age 18-34 at 44.5 per 100,000:

Because of concerns about reported cases of suicide in association with the newer antidepressants, the FDA required a re-evaluation of all prior double blind placebo controlled clinical trials conducted on children and youth conducted during the FDA approval process [33]. The selective serotonin reuptake inhibitor (SSRI) antidepressants were re-evaluated including fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro). In reports issued by the FDA (e.g. [26]) four other potentially stimulating antidepressants were found to produce similar adverse behavioral and mental effects and were included in the group: venlafaxine (Effexor), mirtazapine (Remeron), bupropion (Wellbutrin or Zyban) and nefazodone (Serzone). The meta-analysis found that the risk of suicidal ideation and behaviors was doubled for children and youth taking the antidepressants compared to placebo (4% versus 2%) (Citations in full report).

In 2008, the IOM reported that evidence was adequate for the efficacy of exposure-based therapy (a specific modality in “talk therapy”) but inadequate for other psychotherapy or pharmacotherapy treatments. In 2009, the APA reversed its recommendation for prescribing SSRIs for combat-related PTSD and supported exposure-based therapy:

The American Psychiatric Association’s Guideline Watch was issued in 2009, updating rigorous studies published in 2004–2009 on PTSD treatment (Benedek et al., 2009). Evidence supported the efficacy of exposure-based psychotherapy. Contrary to previous clinical practice, routinely prescribing SSRIs with combat-related PTSD was not recommended.

However, the VA/DoD published conflicting guidelines on treatment preference for PTSD in 2010 and 2011:

According to early Department of Veterans Affairs and Department of Defense (VA/DoD) guidelines for Iraq War, a 12-week trial with a SSRI was strongly recommended as first-line treatment for PTSD, and Cognitive Behavioral Therapy (CBT) was only suggested (Kudler & Ruzek, 2010)… VA/DoD guidelines release in January 2011 recommend psychotherapy with exposure and/or cognitive restructuring for significant benefit and cite pharmacotherapy as proving either unknown (antidepressants, anticonvulsants, atypical antipsychotics, prazosin, propranolol, and imipramine) or no benefit (benzodiazepines and typical antipsychotics) (Management of Post-traumatic Stress Working Group, 2010).

. . . Study found that individuals with significant posttraumatic stress symptoms reported that their symptoms were 75% less severe when they were using cannabis compared with when they were not.

Antidepressants also often create the need for sleep medications, commonly prescribed to combat the side effects from SSRIs which have been shown in studies to degrade sleep in efficiency, time, continuity, depth, and wave. This is an example of the issues of cascading prescriptions (detailed in Part 1) when a patient has sleep deprivation.

GABAergic drugs (those that modify the effects of the sedative GABA neurochemical in the brain) are widely prescribed and yet trials have indicated low efficacy, side effects and tolerance issues, addictive potential, as well as adverse effects on neurocognitive functioning. Of the GABA targeting drugs that show efficacy in PTSD research, Eszopiclone (Lunesta by brand name) has shown to improve sleep disturbance but create substantially more health risks for the patient. Side effects include headache, dry mouth, rash, itching, frequent urination, peripheral edema, dizziness, impaired coordination, and daytime drowsiness. Severe side effects include depression, suicidal thoughts, hallucinations, confusion, abnormal thinking, sleep driving and sleep walking, agitation, aggressive behavior, depersonalization, and amnesia. Eszopiclone is classified as a non-BZD sedative hypnotic and decreasing dose can result in withdrawal. Prescribing an addictive drug with suicidal ideation as a side effect to a patient with PTSD is irresponsible and yet common.

Topiramate (Topamax by brand name) is anti-convulsant drug created for seizures, but used off-label for migraines, bipolar, obesity, and alcoholism. It is also prescribed to counter the weight gain from the side effects of anti-psychotic drugs. Despite having serious adverse effects of suicide and encephalopathy, Topiramate is listed in the VA/DOD 2015 Clinical Practice Guideline for the Management of Substance Use Disorders as a “strong” recommendation and is prescribed accordingly.

Beyond Big Pharma’s Cocktail

Emerging research shows that ocytocin, a hormone, and cannabis, a plant derived medication, are promising adjunctive medications to therapy without the adverse side effects of anti-depressant medications:

[Ocytocin] is well known for its pro-social effects and anxiolytic properties and it has been suggested as promising psychological intervention to enhance treatment response in PTSD (Olff et al., 2014).

“One un-controlled, cross-sectional, retrospective self-report study found that individuals with significant posttraumatic stress symptoms reported that their symptoms were 75% less severe when they were using cannabis compared with when they were not (Greer, Grob, & Halberstadt, 2014). Cannabis has been reported to be particularly helpful to persons with severe traumatic intrusions (Bonn-Miller, Boden, Bucossi, & Babson, 2014) and has been shown to help manage hyperarousal symptoms (Bremner et al., 1996).

Therapies which have demonstrated 100% remission of PTSD symptoms with 10-12 weeks of sessions should be compared to a lifetime of prescription drug maintenance with at most a 60% remission.

Cognitive Behavioral Therapy (CBT) and Cognitive Processing Therapy (CPT) are two of the most effective therapies for PTSD and have demonstrated higher remission rates in PTSD than pharmaceutical medications:

CBT usually involves prolonged exposure, repeatedly recalling a traumatic event until emotional response tapers to allow cognitive confrontation of the trauma. Two additional forms of CBT commonly used are cognitive restructuring, the process of verbalizing, challenging, and replacing erroneous thoughts with balanced ones; and stress inoculation training, a process of reducing anxiety and enhancing coping skills. (Lee, E. A. D. 2012.)

Prolonged exposure (PE) sessions promote confronting traumatic memories to replace maladaptive avoidance behaviors. PE sessions have resulted in complete remission of combat induced PTSD symptoms and lesser likelihood of taking anti-psychotic drugs:

Prolonged exposure is recommended as most beneficial even with variance in frequency and number of sessions for veterans with combat-induced PTSD (Benedek et al., 2009). U.S. female veterans (n = 277) and active duty personnel (n = 7) treated with 10 sessions of prolonged exposure treatment were more likely to no longer meet PTSD criteria (OR 1.80, 95% CI = 1.10–2.96) and to achieve total remission of PTSD symptoms (OR 2.43, 95% CI = 1.10–5.37) than those treated with present-centered therapy; the present-centered group was also more likely to be taking an antipsychotic at post- treatment (p = .03) (Schnurr, Friedman, & Engel, 2007).

Cognitive Processing Therapy helps patients modify maladaptive emotions about traumatic experiences and demonstrates efficacy in 40% of patients with remission of PTSD diagnosis criteria and 50% of clients with reduction in PTSD symptoms:

Significant improvement in PTSD, depression, and Cognitive Distortion Scales for self-criticism, self-blame, helplessness, hopelessness, and preoccupation with danger occurred following 7 weeks of intensive CPT therapy (p < .001 all) in a pretest and posttest study of U.S. veterans (n = 99) in a residential PTSD program (Owens, Chard, & Cox, 2008). Com- pared with U.S. Vietnam veterans (n = 50) with similar clinician assessed pretreatment PTSD scores, OIF/OEF veterans (n = 51) demonstrated significantly lower clinician assessed posttreatment PTSD scores (p < .001), even though they attended significantly fewer CPT sessions (p < .01) (Chard, Schumm, Owens, & Cottingham, 2010). Youth and early treatment may make a difference in treatment efficacy. Even more encouraging, 90% of U.S. veterans (6 women, 54 men) assigned to a 12-session cognitive processing therapy (CPT) composed of cognitive and exposure components showed significant improvement despite long-term PTSD- related disability (40% no longer met PTSD criteria and 50% had reliable reduction in PTSD symptoms; p < .001 both) (Monson et al., 2006).

The VA mental health staff offers members both Prolonged Exposure and Cognitive Processing Therapy. The VA also offers medication treatments that may be indicated for a variety of PTSD conditions. There is likely a treatment preference among patients for prescription drugs over evidence-based therapy because of the perceived response effort. Prescription drugs may not be perceived as requiring time off from duty or work, while therapy sessions require lengthy sessions and weekly appointments. However, the daily maintenance of taking numerous prescription drugs and monthly follow-up appointments also require effort and time off from duty and work. Therapies which have demonstrated 100% remission of PTSD symptoms with 10-12 weeks of sessions should be compared to a lifetime of prescription drug maintenance with at most a 60% remission of PTSD symptoms, and with an additional burden of cascading prescriptions and deteriorating physical health. The idea that prescription drug therapy is a quick fix is also negated by the fact that most drugs prescribed for PTSD take weeks to months of use to provide medicinal effects. Stigma of counseling and lack of trained therapists are also barriers to therapy:

antidepressants were found to produce similar adverse behavioral and mental effects and were included in the group: venlafaxine (Effexor), mirtazapine (Remeron), bupropion (Wellbutrin or Zyban) and nefazodone (Serzone). The meta-analysis found that the risk of suicidal ideation and behaviors was doubled for children and youth taking the antidepressants compared to placebo (4% versus 2%)

Lessons From the United Kingdom

In the past twenty years from 2000-2019, the UK armed forces directed different treatment priorities for PTSD than the U.S. which resulted in a significantly better outcome. In 2005, the UK guidelines for PTSD recommended implementing trauma-focused CBT therapy first, and only using an SSRI if CBT therapy was not sufficient. Conversely, in 2006, the US Pentagon medication policy encouraged a preference for SSRIs medications in PTSD. The UK’s treatment preference has correlated with a 2018 rate of 11 per 100,000 suicides in the active armed forces.

The U.S.’s treatment preference for SSRI’s has correlated with a significantly higher 2018 rate of 24.8 per 100,000 suicides in active duty members. This is not simply reflective of the two countries’ populations in general. The UK and U.S. have similar 2018 rates of suicide in civilians ages 17-59 at 20 per 100,000 in the UK, and 18.2 per 100,000 in the U.S. Among veterans, the UK’s unofficial data in the press reports a much lower number of suicides at 75 veteran suicides in 2018, while the U.S. VA/DoD officially reported 6,139 veteran suicides in 2017. The UK Department of Defence reports that military member suicide is a rare event with a total of 306 suicides in the armed forces from 2000-2019, and subsequently the UK does not have a veteran suicide tracking system. As of 2020, the research and data suggest that the U.S. military suicide rate associated with PTSD has been highly exacerbated by a 15-year delay in implementing guidelines across both active duty members and veterans that prioritize evidence-based CBT therapy over pharmaceutical medications. (All stats are cited in full report).

The total pharmaceutical load on the modern U.S. soldier will continue to result in over 6,000 veteran suicides per year until polypharmacy screening and mitigation is implemented and prioritized at every Veterans Health Administration program. This recommendation also has implications for the mental health epidemic for the civilian population in America.

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