Pharmacological Misinformation Foisted on Unsuspecting Public

An article from January is making the rounds again. One in nextgov's exposé-like series on America's Broken Warriors, it highlighted the fact that 20% of U.S. active duty troops are on psychotropic medications. While this may not be a good thing, the article was filled with erroneous information about specific psych meds and general scare-mongering from antipsychiatry "experts" pitching their books. Let's take a look.

Military's drug policy threatens troops' health, doctors say

By Bob Brewin 01/18/2011

Army leaders are increasingly concerned about the growing use and abuse of prescription drugs by soldiers, but a Nextgov investigation shows a U.S. Central Command policy that allows troops a 90- or 180-day supply of highly addictive psychotropic drugs before they deploy to combat contributes to the problem.

The CENTCOM Central Nervous System Drug formulary includes drugs like Valium and Xanax, used to treat depression, as well as the antipsychotic Seroquel, originally developed to treat schizophrenia, bipolar disorders, mania and depression.

1. Valium (diazepam) and Xanax (alprazolam) are not used to treat depression. These sedative-hypnotic benzodiazepine medications are primarily used to treat anxiety disorders.

2. The atypical antipsychotic Seroquel (quetiapine) was originally developed to treat schizophrenia, although now it is prescribed for bipolar disorder and major depression. Off-label usage of quetiapine, including as a sleep aid, is controversial and I won't be discussing it further here. That topic could easily take up several posts of its own.

The article continues:

A June 2010 internal report from the Defense Department's Pharmacoeconomic Center at Fort Sam Houston in San Antonio showed that 213,972, or 20 percent of the 1.1 million active-duty troops surveyed, were taking some form of psychotropic drug: antidepressants, antipsychotics, sedative hypnotics, or other controlled substances.

Dr. Grace Jackson, a former Navy psychiatrist, told Nextgov she resigned her commission in 2002 "out of conscience, because I did not want to be a pill pusher." She believes psychotropic drugs have so many inherent dangers that "the CENTCOM CNS formulary is destroying the force," she said.

Here we see Dr. Jackson's antipsychiatry agenda first established. All psych drugs are bad. Also note that Dr. Jackson resigned in 2002, before the war in Iraq began on March 20, 2003. So she doesn't have first hand experience with current prescribing practices or the effects of these medications on troops in Iraq and Afghanistan, which is what the article is about.

We also have quotes from one of the leading antipsychiatry advocates, Dr. Peter Breggin:

Dr. Peter Breggin, an Ithaca, N.Y., psychiatrist who testified before a House Veterans Affairs Committee last September on the relationship between medication and veterans' suicides, said flatly, "You should not send troops into combat on psychotropic drugs." Medications on the CENTCOM CNS formulary can cause loss of judgment and self-control and could result in increased violence and suicidal impulses, Breggin said.

Dr. Breggin's credibility as an expert witness has been repeatedly questioned, however. I agree that mentally ill troops should not be sent into combat, but will also point out that untreated and unmedicated psychiatric disorders in a war zone can cause increases in violence and suicidal behavior.

Back to Dr. Jackson:

Jackson, the former Navy psychiatrist, now has a civilian practice in Greensboro, N.C. She said at least one drug on the CENTCOM formulary -- Depakote, an anticonvulsant, which military doctors prescribe for mood control -- carries serious physical risks for troops.

Really? Depakote (valproic acid) is an antiseizure medication also used to treat bipolar disorder. I would like to see statistics on how frequently it's prescribed for "mood control" in soldiers without bipolar disorder.¹

Depakote is toxic to certain cells, including hair cells in the ears, and can lead to hearing loss. Troops in a howitzer battery who already run the risk of hearing loss should not take Depakote, she said.

3. Depakote is certainly not without its adverse effects, but hearing loss is an extremely rare side effect.² In a study of 21 patients taking valproic acid (VPA) to control seizures, there were no differences in hearing thresholds between 125 and 16,000 Hz compared to age- and sex-matched controls (Incecik et al., 2007). In addition, there was no relationship between duration or dosage of drug and hearing levels.

The medication also can cause what she calls "cognitive toxicity," also known as Depakote dementia, impairing a person's ability to think and make decisions. Jackson said that while Depakote has been investigated as an adjunct therapy for cancer, its use has been limited due to the drug's effects on cognition.

4. Contrary to the notion of "Depakote dementia", VPA has been recognized for its potential to treat Alzheimer's disease (Nalivaeva et al., 2009; Zhang et al., 2010). VPA is a histone deacetylase (HDAC) inhibitor that might be able to prevent amyloid-beta aggregation in Alzheimer's disease by increasing the expression of clusterin, or apolipoprotein J (Nuutinen et al., 2010). This would in turn prevent the accumulation of amyloid plaques, a pathological feature in the brains of those with Alzheimer's.

While it's possible that VPA could produce impairments in some cognitive domains, proper studies are difficult because you have to control for the length of illness in untreated patients (since cognitive deficits can be caused by the disorder itself). One such report on currently medicated (n=33) and currently unmedicated (n=32) participants with bipolar depression failed to find group differences in visual memory and sustained attention (Holmes et al., 2008). Unfortunately, this study collapsed across participants on lithium and valproic acid. Further, the groups weren't matched on age, sex, and depression scores. Finally, the medicated individuals were more depressed, which might be expected to worsen performance on its own.

A double-blind cross-over design in healthy controls administered a relatively high dose of VPA for two weeks (800 mg the first week, 1,000 mg the second). There were no changes in memory, concentration, perceptual speed, motor speed, and subjective ratings relative to placebo (Trimble & Thompson, 1981). The drug did, however, slow response times in a category decision task. A review of the literature on cognition and anticonvulsants concluded: "Overall, deficits are subtle, especially in the therapeutic range" for valproic acid (Goldberg & Burdick, 2001). Not exactly a ringing endorsement for cognitive toxicity and Depakote dementia.

On to the next drug:

The antidepressant Wellbutrin, also on the CENTCOM formulary, likely poses a long-term risk of Parkinson's disease, especially for older troops, said Jackson, author of Drug-Induced Dementia: A Perfect Crime (AuthorHouse, 2009).

5. I found no published, peer-reviewed evidence that the antidepressant Wellbutrin (bupropion) increases the long-term risk of developing Parkinson's disease. [Guess we'll have to buy her book to find out why she said that.] Bupropion is a norepinephrine-dopamine reuptake inhibitor, unlike the better known selective serotonin reuptake inhibitors (SSRIs). A few reports have actually recommended buproprion for treating depression, panic disorder, and compulsive behaviors in patients with Parkinson's disease (Benincasa et al., 2010; Gebhardt et al., 2008; Załuska & Dyduch, 2011), although the lack of double-blind placebo-controlled studies was acknowledged.

I did find a few case reports that bupropion can induce a parkinsonian-like condition within a week or two, especially in elderly patients, that abates upon discontinuation (Szuba et al., 1992; Cheng et al., 2009). This is not the same thing as increasing long-term risk for Parkinson's in "older troops" given the drug.

I think I'll stop for now. The rest of the article covers the addiction potential of alprazolam (well-supported by the literature), the dangers of quetiapine (an issue not discussed here), and an unsupported statement from Jackson that "Seroquel has the addictive potential of opioids, such heroin."

Although these psychotropic medications are not without their risks and adverse side-effects, neither are they a societal evil capable of producing a military force of deaf, demented, and parkinsonian troops.


Footnotes

¹ VPA has been shown to be ineffective in treating post-traumatic stress disorder (Davis et al., 2008; Hamner et al., 2009).

² The ototoxicity of VPA was not mentioned in this 233 page book on Otoxtoxicity (PDF) or in this review of ototoxic drugs.


References

Benincasa D, Pellicano C, Fanciulli A, Pontieri FE. (2011) Bupropion abates dopamine agonist-mediated compulsive behaviors in Parkinson's disease. Mov Disord. 26:355-7.

Cheng WC, Liu CM, Hsieh MH, Hwang TJ. (2009). Bupropion-related parkinsonism and dystonia. J Clin Psychopharmacol. 29:616-8.

Gebhardt S, Röttgers H, Bäcker A, Schu U, Krieg JC. (2008). Treatment of panic disorder with bupropion in a patient with Parkinson's disease. J Clin Pharm Ther. 33:575-7.

Goldberg JF, Burdick KE. (2001). Cognitive side effects of anticonvulsants. J Clin Psychiatry 62 Suppl 14:27-33.

Holmes MK, Erickson K, Luckenbaugh DA, Drevets WC, Bain EE, Cannon DM, Snow J, Sahakian BJ, Manji HK, & Zarate CA Jr (2008). A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Bipolar disorders, 10 (7), 806-15 PMID: 19032712

Incecik F, Akoglu E, Sangün O, Melek I, & Duman T (2007). Effects of valproic acid on hearing in epileptic patients. International journal of pediatric otorhinolaryngology, 71 (4), 611-4 PMID: 17270285

Nalivaeva NN, Belyaev ND, Turner AJ. (2009). Sodium valproate: an old drug with new roles. Trends Pharmacol Sci. 30:509-14.

Nuutinen T, Suuronen T, Kauppinen A, Salminen A. (2010). Valproic acid stimulates clusterin expression in human astrocytes: Implications for Alzheimer's disease. Neurosci Lett. 475:64-8.

Szuba MP, Leuchter AF. (1992). Falling backward in two elderly patients taking bupropion. J Clin Psychiatry 53:157-9.

Thompson PJ, Trimble MR (1981). Sodium valproate and cognitive functioning in normal volunteers. British journal of clinical pharmacology, 12 (6), 819-24 PMID: 6803819

Załuska M, Dyduch A. (2011). Bupropion in the treatment of depression in Parkinson's disease. Int Psychogeriatr. 23:325-7.

Zhang XZ, Li XJ, Zhang HY. (2010). Valproic acid as a promising agent to combat Alzheimer's disease. Brain Res Bull. 81:3-6.