SEX, [pain] DRUGS, and ROCK & ROLL

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R and B Sex & Drugs


Although a focus of pain management is to improve functionality and quality of life, and choice of regimens can be “gray”, side effects from medications are more predictably printed in black and white.  The discussion of sexual dysfunction associated with medications used for pain management is often cast aside because of discussion comfort levels among patients and clinicians.  It is however an important topic.  As promised, this is Part 2 of our original post, Chronic Pain, Sex, Passion, and Shades of Grey.

Below, three guest bloggers, Drs. Alexandra H. Kawola and Thien C. Pham, PGY1 General Practice and PGY2 Pharmacy Pain Residents respectively, and Ms. Erika F. Prouty, Pharm.D. Candidate, 2015 delineate various pain medication classes commonly used that are attributable to sexual dysfunction and loss of libido. This post also suggests certain ways to overcome these pharmacological obstacles.  Included in their discussion are antidepressants, anticonvulsants and opioids.

Antidepressants

Antidepressant use has become a mainstay for treatment for neuropathic, and more recently even generalized pain. Sexual side effects have emerged as a growing concern among patients prescribed antidepressants. The incidence of sexual side effect, however, is difficult to estimate because the cause of sexual dysfunction can be associated with the disease state, interpersonal difficulties and medications. Few quality studies have focused on the nature of antidepressant associated sexual dysfunction, however there are some proposed mechanisms and remedies. Understanding the reason behind dysfunction is important as decreased libido, erectile dysfunction and delayed or absent orgasm may lead to poor adherence and ultimately poor therapy outcomes.

Multiple pharmacological mechanisms have been proposed and are neurotransmitter-specific based. Serotonin, norepinephrine, dopamine, prolactin and nitric oxide are all substances that have been studied as probable causes for sexual dysfunction due to antidepressant use.

The following are proposed ways to manage sexual dysfunction.

  1. Wait for drug tolerance to develop
  2. Dose reduction
  3. Switch antidepressants  – Lowest rates of sexual side effects include nefazodone, bupropion and mirtazapine
  4. Augmentation drug-induced sexual dysfunction with an “antidote”

It is important for patients to be reassured that sexual dysfunction is generally reversible when the medication is discontinued.  One strategy for dysfunction is to wait for tolerance to develop or lowering the dose, however symptoms do not always resolve. For this reason, this article will explain how to select antidepressants that are less likely to cause sexual dysfunction, or augment therapy if switching is not a therapeutic option.

Serotonin

Evidence linking serotonin to sexual response is difficult because there are no agents which are exclusively selective to serotonin. Animal studies, however, have demonstrated there are different roles between different serotonin receptors. It has been proposed that 5-HT1a receptors facilitate sexual behaviors, whereas 5-HT2c/1b inhibits sexual behaviors. Based on this mechanism, one proposed regimen to combat sexual dysfunction is to augment therapy with an antidote.

  1. Anti-serotonergic Drugs: Antidotes that have been studied, express 5-HT2 antagonistic effects such as the antihistamine, cyproheptadine. Cyproheptadine has been given to patients on “as needed”, or perhaps better phrased “as desired” basis and also by regularly scheduled dosing. Case reports attest to its efficacy, specifically with anorgasmia (lack or orgasm), however concern has been raised that therapeutic effects of the antidepressant may be diminished. Additionally, use of cyproheptadine is often limited due to excessive sedation.

Dopamine

Dopamine neurotransmission has been directly associated with sexual arousal. This has been evident by increased libido in patients receiving L-dopa for Parkinson’s Disease. Commonly used antidepressants regulate dopamine to different effects which offers an explanation as to why some antidepressants cause more sexual dysfunction than others.Switch to a different antidepressant: Paroxetine has a strong affinity for serotonin receptors and very limited effect on dopamine. Several other specific serotonin reuptake inhibitors (SSRIs) cause small amounts of dopamine reuptake inhibition. This elevation of dopamine can lead to increased sexual arousal. For this reason, consider avoiding use of paroxetine in patients affected by or concerned with sexual dysfunction.

  1. Switch to a different antidepressant: Paroxetine has a strong affinity for serotonin receptors and very limited effect on dopamine. Several other specific serotonin reuptake inhibitors (SSRIs) cause small amounts of dopamine reuptake inhibition. This elevation of dopamine can lead to increased sexual arousal. For this reason, consider avoiding use of paroxetine in patients affected by or concerned with sexual dysfunction.
  2. Switch or augment therapy: Bupropion is an atypical antidepressant that has been associated with improvement in sexual function. Bupropion has dopamine reuptake inhibition properties which could explain the lack of sexual dysfunction and perhaps enhanced function. Combination use of bupropion with an SSRI is common and often well tolerated, however incidence of adverse reactions and drug interactions should be considered.
  3. Augment therapy: Addition of dopamine agonist, including dextromethorphan, low dose dextroamphetamine and amantadine have also been studied to decrease sexual dysfunction associated with antidepressants. Addition of these agents have demonstrated a diminished orgasm threshold and enhanced libido.

Prolactin

Increased serotonin and decreased dopamine have been noted to increase prolactin release from the hypothalamus. Elevated prolactin levels have been associated with diminished sexual desire and performance. Antidepressants with strong serotonergic activity and low dopaminergic activity can cause elevated prolactin levels, increasing risk for sexually related side effects.

  1. Switch or augment: In order to decrease risk of sexual side effects, it is recommended to avoid antidepressants with strong serotonergic activity that is devoid of dopamine reuptake inhibition. Alternatively, as stated above, elevated prolactin could be combated through use of dopaminergic agents, such as bupropion.

Treatment of sexual dysfunction associated with antidepressants is an important issue but still lacks strong evidence. In order to increase quality of life and adherence in these patients, sexual side effects should be assessed and addressed.

Anticonvulsants

There has long been evidence associating anticonvulsant agents and sexual dysfunction in both men and women.  Most documentation has been reported in patients with epilepsy, a population who are likely the commonest users of these agents to control their disorder.  However, anticonvulsants are also frequently used in patients suffering from chronic neuropathic pain since they exhibit pain relief properties by varying pharmacological mechanisms.  Although it is not known exactly how these agents help reduce neuropathic pain, it is suggested they do so mainly by blocking pain signals from the body’s central nervous system.  Most studies relating anti-convulsants with sexual dysfunction are with the older agents, such as phenytoin, phenobarbital, carbamazepine, and valproic acid.  These agents have been shown to decrease libido, caase anorgasmia, and a decrease in testosterone levels (testosterone is linked to sexual drive in both men and women).  They even have been associated with sperm abnormalities in men.  These agents are also what are known as ‘hepatic-enzyme inducers’ through Phase I (CYP 450) metabolism, which stimulates the production of sex-hormone binding globulin (SHBG), a glycoprotein that binds to sex hormones and inhibits their ability to function.   An increase in SHBG therefore decreases the amount of free testosterone, a side effect of these older agents.

So what options are available for those patients concerned with these side effects?  Newer agents, such as lamotrigine, gabapentin, pregabalin, and levetiracetam do not undergo Phase I metabolism.  These agents have had little to no association with the sexual dysfunction side effects as compared to the older agents. In fact, there have been some reports of priapism from both gabapentin and pregabalin, so caustion needs to be exhibited here, as this is considered a medical emergency.  For patients who require continued use of anticonvulsant agents for neuropathic pain, the newer agents could serve as appropriate alternatives and patients may opt to speak with their providers if sexual dysfunction is a concern.

Opioids

Chronic use of opioids and their effects on the hypothalamic-pituitary-gonadal axis (HPGA) and endocrine function has been well established and published over the years.  Some specific symptoms from these hormonal effects consist of decreased libido and activity, erectile dysfunction, small or shrinking testes, decreased sperm count (leading to possible infertility), and hot flashes. Other less specific symptoms include decreased energy/motivation/initiative/self-confidence, depressed mood, poor concentration and memory, and diminished physical performance. As a result of these hormonal side effects from long-term opioid therapy, quality of life may be diminished for a patient living with a chronic pain syndrome.

As outlined in a previous PainDr.com blog, Opioid-Induced Androgen Deficiency (OPIAD), the HPGA is a sophisticated biochemical system that regulates the release of sex hormones through an endogenous negative feedback mechanism originating from the hypothalamus.  Figure 1 illustrates the effects of opioids on the HPGA inhibiting the release of gonadotropin-hormone releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH),plus testosterone and estrogen.  The management OPIAD may include:

  1. Discontinuation of opioid therapy
  2. Reducing the opioid dose
  3. Opioid rotation
  4. Hormone replacement therapy

Figure 1:  Effects of opioids on the endocrine system

HAPA figureMale patients who complain of pain to the point where it is debilitating and are “unable to function”, often are co-prescribed sildenafil citrate (Viagara®).  It also is important to obtain testosterone levels and replace if necessary, because low testosterone also places male patients at risk of osteoporosis which generally is not tested routinely in males.  But, resultant decreased bone density in this population because of low “T” presents the inherent risk of bone fractures.  Considering that one may be using chronic opioid therapy for failed back syndrome, spinal fractures could be extremely debilitating.

So there you have it.  At least three major drug classes commonly used to treat various pain syndromes can clearly affect sexual function.  This coupled with pain itself, exhaustion, and mood can all have a negative impact a patient’s well-being, self-worth, and overall life pleasure.  It is for all of these reasons that we encourage first and foremost, an educated clinician and patient.  Also, patients with chronic pain should consider healthy life style choices, exercise, alternative medications if appropriate, couples counseling, and most of all a positive outlook and hope.

As always, comments and discussions are enthusiastically welcomed.

Our Guest Authors

Left to Right Dr. Ali Kawola; Dr. Thien Pham; Ms. Erika Prouty
Left to Right
Dr. Ali Kawola; Dr. Thien Pham; Ms. Erika Prouty

Alexandra Hubbard Kawola, Pharm.D.  better known as Ali, is a PGY-1 Pharmacy Resident at the Stratton VA Medical Center in Albany, NY. She completed her Doctor of Pharmacy degree at Albany College of Pharmacy and Health Sciences in Albany, NY.  She has taken an interest in ambulatory care pharmacy and hopes to become a board-certified ambulatory care pharmacist. 

Thien Cong Pham, B.S., Pharm.D. is a PGY2 Pain & Palliative Care Pharmacy Resident at the Stratton VA Medical Center in Albany, NY.  A Navy Veteran, Dr. Pham completed a PGY1 Pharmacy Practice Residency at Veterans Affairs Medical Center in Palo Alto, CA.  Prior to receiving his Doctor of Pharmacy at Touro University California in Vallejo, CA, he received his Bachelors Degree in Biochemistry with a Medical Sciences emphasis from the University of California Riverside and Associate of Science from Riverside City College in Riverside, CA.

Erika Prouty, BS Bio, BS Environmental Sci. is a Student Pharmacist studying with the Western New England University, College of Pharmacy, Class of 2015. She is currently part of the Mini-Residency program at the Stratton VA Medical Center in Albany, NY; a program designed to mimic the longitudinal and clinical aspects anticipated as a PGY1 Pharmacy Resident. In 2011, she received her Bachelors in Biology and Bachelors of Environmental Science from Westfield State University. In 2008, she received her Associates in Liberal Arts and General Studies from Springfield Technical Community College. Erika likes walks on the beach and traveling to other countries.

The content herein is the opinion of the authors and was not prepared as part of their government duties, nor was this reviewed or approved by any government agency.

REFERENCES:

  1. Zajecka J, Fawcett J, Schaff M, et al: The Role of Serotonin in Sexual Dysfunction: Fluoxetine-associated orgasm dysfunction, J Clin Psychiatry 52: 163-164, 1991.
  2. Prabhakar, D, Balon R. How do SSRIs cause Sexual Dysfunction? Current Psych. 9(12);30-34, 2010.
  3. Rosen RC, Lane RM, Menza M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol. 1999 Feb;19(1):67-85.
  4. Harden, Cynthia L., MD. Sexualiy in Men and Women With Epilepsy. CNS Spectr. 2006; 11:8 (Suppl 9): 13-18.
  5. Macphee GJA, Larkin JG, Butler E, Beastall GH, Brodie MJ. Circulating Hormones and Pituitary Responsiveness in Young Epileptic Men Receiving Long-Term Antiepileptic Medication. Epilepsia. 1988. 29 (4): 468-475.
  6. Herzog AG, Drislane FW, Schomer DL, et al. Differential Effects of Antiepileptic Drugs on Sexual Function and Reproductive Hormones in Men with Epilepsy: Interim Analysis of a Comparison between Lamotrigine and Enzyme-Inducing Antiepileptic Drugs. Epilepsia. 2004. 45 (7): 764-768.
  7. Lossius MI, Tauboll E, Mowinckel P, et al. Reversible Effects of Antiepileptic Drugs on Reproductive Endocrine Function in Men and Women with Epilepsy- A Prospective Randomized Double-Blind Withdrawal Study. Epilepsia. 2007. 48 (10): 1875-1882.
  1. Bhasin S1, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.
  2. Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002 Oct;3(5):377-84.
  3. Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009 Feb;25(2):170-5.
  4. Smith HS, Elliott JA. Opioid-induced androgen deficiency (OPIAD). Pain Physician. 2012 Jul;15(3 Suppl):ES145-56.
  5. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013 Mar;126(3 Suppl 1):S12-8.
  6. Paredes RG. Opioids and sexual reward. Pharmacol Biochem Behav. 2014 Jun;121:124-31.
  7. World Health Organization. Patterns and consequences of the use of amphetamine-type stimulants (ATS). Technical Briefs on amphetamine-type stimulants (ATS).  Available at: http://www.who.int/hiv/pub/idu/ats_tech_brief/en/

 

 

 

 

5 thoughts on “SEX, [pain] DRUGS, and ROCK & ROLL

  1. Nice post..!! This elevation of dopamine can lead to increased sexual arousal. For this reason, consider avoiding the use of paroxetine in patients affected by or concerned with sexual dysfunction I agree with you. I recently got this article which is very informative for me. I loved it. It is the really great article.

  2. Dr. Fudin thank you very much for your hard work and thanks to the Guest Authors for their various suggestion’s on ways to overcome sexual dysfunction for people that suffer from chronic pain.
    I’m sure this will help many chronic pain sufferers find a way to solve sexual dysfunction that antidepressants , anticonvulsants and opioids bring about . However for some chronic pain sufferers like myself I cant take antidepressants or anticonvulsants because of the side effects . I take the lowest dose possible of a long acting opioid that best helps me control my chronic pain for the past 28 years.
    The story from Kurt sounds a lot like my cervical pain from DDD.

    Its not so much sexual dysfunction for me and I’m sure a lot of people in chronic pain like me but my age category that seems to have the most effect . The fact is most but not all woman my age I’m no longer attracted to and I’m sure this is true for a lot of people my age, I will be 59 this June. As we age our bodies and looks also change. I’ve found woman no longer find me a attractive guy like I once was when I was younger .

    I was grocery shopping last week and heard my name called out , this woman approached me and I didn’t recognize her. She was very nice and said its me a woman I dated back in 1990, seems it wasn’t that long ago but indeed it was 25 ago years since I’ve seen this woman and her looks changed dramatically . I could not believe how drastic her looks changed, although I found out she didn’t take care of herself after we dated and that made her look older than normal.
    So beings though were talking about sexual dysfunction and telling it like it is , how does a person like myself deal with no longer being attracted to most woman my age and they no longer attracted to me.
    I do stay in good shape fast walking 3 miles most every day , but this doesn’t seem to change the fact that age has caught up with me. This chronic pain thing changed my life and got in the way of me meeting that special person and having a family. Its not my intentions to offend anyone , I’m just stating the facts as to what is true and till this day has kept me from having a normal life and relationship with that special person. And time is passing by fast, it seems the older I get time passes much quicker.

    1. Dear Mark,

      Of course you will be more sexually attracted to a younger woman than a woman who is closer to your age. As a woman who is 50 years old I find a 30 year old man more visually Attractive than a 50 year old man. If all you seek is is a roll in the sack with a woman and you can find a willing partner by all means go for it.

      As for me, even though the 30 year old man is sexier than the 50 year old and I would have no trouble finding a willing partner, I prefer to have sex with a man closer to my own age. First I am interested in more than just a sexual relationship. Sex lasts 30 minutes on average so what about the remainder of day? Connection, shared interests, same generation are important. Secondly I would be a bit creeped out having sex with a man who could be my son. Too Norman Bates for me. However this aspect has not seemed to bother men.

      Life is to be enjoyed and sex is just one item on the menu of life. Have a complete meal! Also consider looking inward. Are you having a hard time accepting the fact that you have aged? Peter Pan syndrome? Do you view a woman more as an accessory rather than an interval part of your life?

      Lastly I prefer to wake up next to a man closer to my age so that the relationship is more a relationship of equals. I live in a 50 year old body and I prefer my lover to live in the same.

  3. I hope doesn’t sound a dumb question. lol
    We always hear about how opioids affect male hormones but we hear nothing about any affects on women.
    Do these medications affect female hormones in any way? We know menopause does affect women and they can use HRT for that, but my questions is? Does opioid pain medication deplete the female hormones at all? I haven’t been able to find anything on this, so I am guessing no?
    I’m only asking about opioids. Not any of the other classes of medications mentioned above.
    Thanks. 🙂 I’m sure many women have been wondering as well.

  4. In the mid eighties, and this is before I was injured I was admitted voluntarily to a PTSD unit in Little Rock AR. This was the premier PTSD unit for Vietnam vets. When we arrived, there was a tenuous process of just getting in the program. “Will you take an antidepressant?” I said, “Hell yea, I wanna sleep, and get back to the normalcy of LIFE.” I was an RN in a E. Texas hospital. Lot of stress, but I was only in my late thirties at the time and unmarried. Things were different. No girlfriends, didn’t care. Sick to death of dreaming of war. So,I took the VAs prozac. AUTOMATIC, SUPERMAN. I thought, “This is the best thing that has happened to me.” Not depressed, and many female sexual partners. NOT bragging, but it was the best thing that had happened in years. THEN, the crash. Three months later I woke up and the world could go to hell. So, off the prozac, and then the switching up of antidepressants. All of them, well, SSRI antidepressants. Nothing worked. Thing is, I worked my way through the depression through tons of group therapies. Several models.
    I was married to the woman who has stuck with me to this day. In 99, as some of you know injured in a psych unit while admitting a “meth head, that was also a schitzophrenic”. Well, didn’t feel like sex, the pain was too great. The meds, they were just an added weight to the decreased sexual activity that accompanied the injury. This was important to me. Heck, my wife said, “Darlin, we have had a wonderful sex life and that’s just the breaks.” Very understanding woman.
    But, we didn’t give up. I DID NOT TAKE EDs but one time. Got a horrible headache, itching. It was like a tripple dose of a vitamin I once took, that I cannot call the name. Horrible side effects. So, back to the group therapies, but this time, between me and my wife. What could help? We thought, “Why not try,, well, our imaginations?” So, we did. I’m not going to get into this, haha, very personal. BUT, one’s mind can really cut through all that mess of increased opoids, and other meds that one has to take while going through a lifetime injury. I will tell you this. When we would go out to eat, or on a date, she would spice up her “window dressing”. NOW, can’t push down “Oak trees anymore”, at my age, but it ain’t ALL GONE, lol………………this article really got me thinking. To yall out there that experience sexual dysfunction, spicing up ones life can cut through the pain. Just go back to group therapy…………….pain doesn’t leave,but my mind is off of it for a few hours, lolol,,,,,,,ok, “few minutes”. Thanks Dr. Jeff!!!!

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