Sep
28
2013

Sleepless Nights

Sleeping problems (insomnia) are very common. About 10% of the population suffers from chronic insomnia; 30% of the population suffers from occasional sleep problems. In a large outpatient population of a clinic consisting of 3500 patients who had at least one major clinical condition, 50% complained of insomnia, 16% had severe symptoms, 34% had mild symptoms (Ref.1). Insomnia is more common among women, and older people as well as in people with medical or psychiatric illnesses. Long-term studies have shown that the same insomnia problems persist throughout many years. It is not possible to offer a simple remedy for insomnia, because insomnia is a complex problem. Here I will discuss some of the causes of insomnia and also discuss some of the treatment options.

Symptoms of insomnia

The person who suffers from insomnia will usually state that they have problems falling asleep. Worries of the day suddenly circulate through their thoughts and they toss and turn nervously looking at the clock from time to time and getting more and more anxious that they cannot sleep. Others fall asleep OK, but in the middle of the night they wake up perhaps to visit the restroom, but then they cannot go back to sleep. Others wake up 2 hours before their normal alarm clock time and they feel their stomach rumbling making it impossible to fall back to sleep. Older people with chronic diseases and general poor health suffer more from insomnia. In this setting insomnia may be more related to the underlying disease rather than old age. Psychiatric disorders also are associated with more insomnia. Treat the underlying psychiatric illness, and the insomnia disappears.

Although insomnia is a sleep disturbance during the nighttime, people who are affected with this complain of daytime fatigue, of overstimulation, yet they catch themselves making frequent mistakes, and their inability to pay attention gets them involved in accidents and falls. Longitudinal studies have shown (Ref. 1) that people with chronic insomnia are more likely to develop psychiatric disease, such as major depression,  anxiety disorder and alcohol and substance abuse. Unfortunately these disorders can by themselves again cause insomnia, which reinforces chronic insomnia. Insomnia leads to poorer social and physical functioning, affects emotions, leads to a lack of vitality and physical endurance, contributes to worsening of pain and can affect general and mental health.

Research about insomnia

Much has been learnt from sleep studies using polysomnography monitoring during a full night’s sleep. These studies have been used mainly as a research tool. In such studies eye movements, brain wave activity, muscle activity, chest movements, airflow, heart beats, oxygen saturation and snoring (with a microphone) are all simultaneously recorded. This way restless leg syndrome, sleep apnea, snoring, seizure disorders, deep depression etc. that can all lead to insomnia can be diagnosed and separated from insomnia. The stages of sleep (wakefulness, stage 1 to 3 sleep and the REM sleep stage) can also be readily measured using polysomnography (Ref.2). According to this reference the majority of insomnia cases do not need this complex procedure done.

Sleepless Nights

Sleepless Nights

Causes of insomnia

Traditionally insomnia cases are classified into primary insomnia and secondary insomnia. Secondary insomnia is caused by all of the factors discussed below. When they are dealt with, we are left with cases of primary insomnia.

The following medical conditions can cause insomnia: heart disease, pulmonary diseases like asthma and chronic obstructive pulmonary disease (COPD); gastrointestinal disease like liver cirrhosis, pancreatitis, irritable bowel syndrome, ulcers, colitis, Crohn’s disease; chronic kidney disease; musculoskeletal disease like arthritis, fractures, osteoporosis; neurodegenerative disease like MS, Parkinson’s disease, Alzheimer’s disease; endocrine disease like diabetes, hyper- or hypothyroidism, adrenal gland fatigue and insufficiency; and chronic pain conditions. Also, psychiatric conditions like major depression, schizophrenia and anxiety disorders can cause insomnia.

This list in not complete, but it gives you an idea of how complex the topic of insomnia is.
The physician who is seeing a patient with insomnia needs to rule out any of these other causes of insomnia to be certain that the only condition that is left to treat in the patient is insomnia itself. The other diagnoses have to be dealt with separately or else treatment of insomnia will fail.

Ref. 1 points to a useful model of how to think about causation of insomnia: there are three points to consider, namely predisposing, precipitating, and perpetuating factors. Let’s briefly discuss some of these.

Predisposing factors

We are all different in our personal make-up. If you are well grounded, chances are you are not susceptible to insomnia. Anxious persons or persons who have been through a lot of negative experiences in life will have personality traits that make them more prone to insomnia. Lifestyle choices such as late nights out, drinking with the buddies in a bar (extreme circadian phase tendencies) will have an impact on whether or not you develop insomnia.

Precipitating factors

A situational crisis like a job change or the death of a loved one can initiate insomnia.  However, there could be a medical illness such as a heart attack, a stroke or the new diagnosis of a psychiatric illness that has become a precipitating factor. Sleep apnea and restless leg syndrome belong into this group as well as would the stimulating effect of coffee and caffeine containing drinks. Jet lag and nighttime shift work can also be precipitating factors.

Perpetuating factors

Daytime napping to make up for lost sleep the night before can undermine sleep initiation the following night, which can lead to a vicious cycle. Similarly, the use of bedtime alcoholic drinks leads to sleep disruption later that night and can become a perpetuating factor, if this habit is maintained. Even the psychological conditioning of being anxious about whether or not you will fall asleep easily or not the next night can become a perpetuating factor.

I will return to this classification and the factor model of causation of insomnia when we address treatment options.

Drugs that can cause insomnia

One major possible cause for insomnia  can be side effects from medications that patients are on (would belong to the ‘perpetuating factors’ among causes). Physicians call this “iatrogenic insomnia”. The antidepressants, called selective serotonin reuptake inhibitors (SSRI’s) like Prozac are particularly troublesome with regard to causing insomnia as a side effect. Other antidepressants like trazodone (Desyrel) are used in small doses to help patients with insomnia to fall asleep. Some asthmatics and people with autoimmune diseases may be on prednisone, a corticosteroid drug. This can cause insomnia, particularly in higher doses; so can decongestants you may use for allergies; beta-blockers used for heart disease and hypertension treatment; theophylline, an asthma medication and diuretics. Central nervous stimulants like caffeine or illicit drugs can also cause insomnia. Hormone disbalance in general and hyperthyroidism specifically as well as Cushing’s disease, where cortisol levels are high will cause insomnia.

Treatment of insomnia

So, how should the physician approach a patient with insomnia? First it has to be established whether there is secondary insomnia present due to one of the predisposing, precipitating or perpetuating factors. In other words, is there secondary insomnia due to other underlying illnesses? If so, these are being addressed first. Lifestyle choices (staying up late every night) would have to be changed; alcohol and drug abuse and overindulging in coffee or caffeine containing drinks needs to be dealt with. Cognitive therapy may be beneficial when mild depression or anxiety is a contributing factor to insomnia.

The remaining insomnia (also medically termed “primary insomnia”) is now being treated.

The following general points are useful to get into the sleeping mode (modified from Ref. 3):

  1. Ensure your bedroom is dark, soundproof, and comfortable with the room temperature being not too warm, and you develop a “sleep hygiene”. This means you get to sleep around the same time each night, have some down time 1 hour or so before going to bed and get up after your average fill of sleep (for most people between 7 to 9 hours). Do not sleep in, but use an alarm clock to help you get into your sleep routine.
  2. Avoid caffeine drinks, alcohol, nicotine and recreational drugs. If you must smoke, don’t smoke later than 7PM.
  3. Get into a regular exercise program, either at home or at a gym.
  4. Avoid a heavy meal late at night. A light snack including some warm milk would be OK.
  5. Do not use your bedroom as an office, reading place or media center. This would condition you to be awake.  Reserve your bedroom use only for intimacy and sleeping.
  6. If you wake up at night and you are wide awake, leave the bedroom and sit in the living room doing something until you feel tired and then return to bed.
  7. A self-hypnosis recording is a useful adjunct to a sleep routine. Listen to it when you go to bed to give you something to focus on (low volume) and you will find it easier to stop thinking.

Drugs and supplements for insomnia

1. In the past benzodiazepines, such as diazepam (Valium), lorazepam (Ativan), fluorazepam (Dalmane), temazepam (Restoril), triazolam (Halcion) and others were and still are used as sleeping pills. However, it was noted that there are significant side effects with this group of drugs. Notably, there is amnesia (memory loss), which can be quite distressing to people such as not remembering that someone phoned while under the influence of the drug, you promised certain things, but you cannot remember the following morning what it was. Another problem is the development of addiction to the drugs with worse insomnia when the drugs are discontinued. Many physicians have stopped prescribing benzodiazepines.

2. There are non-benzodiazepines drugs that are used as sleeping pills (hypnotics), such as Zaleplon (Sonata), Zolpidem (Ambien) and Eszopiclone (Lunesta).  They seem to be better tolerated.

3. Ramelteon, a melatonin agonist, is available by prescription in the US. It probably is the best-tolerated mild sleeping pill and works similar to melatonin, but is more expensive. Chances are that your physician likely would prescribe one of the non-benzodiazepines drugs or Ramelteon for you as they do not seem to be addicting.

4. However, there is an alternative: Many patients with insomnia tolerate a low dose of trazodone (Desyrel), which is an antidepressant with sleep restoring properties. A low dose of 25 to 50 mg at bedtime is usually enough for insomnia. This allows the patient to fall asleep within about 30 minutes of taking it, and sleep lasts through most of the night without a hangover in the morning. Many specialists who run sleep laboratories recommend trazodone when primary insomnia is diagnosed. However, this is still a drug with potential side effects as mentioned in the trazodone link, but 50 mg is only ¼ of the full dose, so the side effects will also be less or negligible.

5. I prefer the use of melatonin, which is the natural brain hormone designed to put us to sleep. Between 1 mg and 6 mg are sufficient for most people. We know from other literature that up to 20 mg of melatonin has been used in humans as an immune stimulant in patients with metastatic melanoma with no untoward side effects other than nightmares and some tiredness in the morning. A review from the Vanderbilt University, Holland found melatonin to be very safe as a sleeping aid. There are several melatonin receptors in the body of vertebrates (including humans), which are stimulated by melatonin.

6. Other natural methods are the use of L-Tryptophan at a dose of 500 mg at bedtime, which can be combined with melatonin. It is the amino acid contained in turkey meat, which makes you tired after a Thanksgiving meal. GABA is another supplement, which is the relaxing hormone of your brain, but with this supplement tolerance develops after about 4 to 5 days, so it is only suitable for very short term use. Herbal sleep aids are hops, valerian extract and passionflower extract. They are available in health food stores.

Conclusion

A lack of sleep (insomnia) is almost a given in our fast paced lives.

When it comes to treatment, all of the other causes of secondary insomnia need to be treated or else treatment attempts would fail. What is left is primary insomnia. This is treated as follows:

We need to review our sleeping habits, lifestyles and substance abuse. Remove what is detrimental to your sleep. Start with the least invasive treatment modalities such as self-hypnosis tapes, melatonin, L-Tryptophan or herbal extracts. Should this not quite do the trick, asks your doctor for advice. The non-benzodiazepines drugs or Ramelteon would be the next level up. It may be that an alternative such as low dose trazodone would be of help. Only, if all this fails would I recommend to go to the more potent sleeping pills (keep in mind the potential for addiction to them).

References

1. David N. Neubauer, MD (John Hopkins University, Baltimore, MD): Insomnia. Primary Care: Clinics in Office Practice – Volume 32, Issue 2 (June 2005)  © 2005, W. B. Saunders Company

2: Behrouz Jafari, MD and Vahid Mohsenin, MD (Yale Center for Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA): Polysomnography. Clinics in Chest Medicine – Volume 31, Issue 2 (June 2010), © 2010 W. B. Saunders Company

3. Jean Gray, editor: “Therapeutic choices”, 5th edition, Chapter 8 by Jonathan A.E. Fleming, MB, FRCPC: Insomnia, © 2008, Canadian Pharmacists Association.

Last edited Sept. 28, 2014

Aug
17
2013

Postpartum Depression

Recently there has been a lot of publicity around the topic of postpartum depression (PPD). Typically the reports originate from a case where depression led to catastrophic consequences. It is sad that it often takes a tragedy before a problem like this is publicly more acknowledged. But sadly reports are often one-sided and are missing vital information about preexisting risk factors that are frequently not picked up by the family doctor. There is often denial on behalf of the mother and family, the mother is getting no support from support groups, even though there are such groups. And swift treatment that would be available is often not given. The results are finally making headlines. Once a mother is desperate and deeply depressed (“psychotic depression”) she is capable of killing the baby, herself and others who are close. PPD affects 15% of mothers (Ref.1); a small percentage of them may have postpartum psychosis, which is the most severe form of PPD.

Risk factors for postpartum depression

In Ref. 1 several risk factors are reviewed that can lead to postpartum depression. For instance, a history of a major depressive episode or anxiety attacks during the pregnancy has been found among mothers who developed PPD. However, there may also have been a history of dysphoria (intense feeling of discontent) before her periods in the past; stressful events during the pregnancy or right after birth. Often there is poor social support or a marital conflict. Other factors are low income, young maternal age or immigrant status with deprivation. A lack of support from the partner can also be a major factor.

Up to 85% of women experience postpartum blues within the first 10 days after the delivery of the baby. Symptoms such as mood swings, fatigue, confusion, tearfulness, mild elation and irritability are common during these initial days following her delivery. Progesterone levels following delivery are decreased for at least one month, sometimes up to 3 months. This leads to sleep problems (insomnia), which coupled with the baby crying in the middle of the night causes more sleep disruption. Abnormal brain wave pattern have been documented on women following the birth of a child.

Only 1 in 500 mothers after birth develop what physicians call “postpartum psychosis”, which is a recognized psychiatric emergency.  The symptoms here are extreme mood swings with confusion, poor judgment, disordered thoughts (“delusions”), paranoia (where they think that someone is after them or it is the baby’s fault that they feel that way). Erratic behavior and impaired functioning are also part of this symptom complex. It is this state that needs to be monitored in a psychiatric unit as it is associated with a high suicide and homicide rate. A psychiatrist with experience in treating PPD needs to treat the patient.

Urbanization leads to a lack of support, which is particularly devastating to new mothers who need all the support they can get. This is reflected in a higher percentage of PPD in urban areas versus the percentage of PPD in more rural areas where there is more family support.

 

Postpartum Depression

Postpartum Depression

Hormone changes with postpartum depression

Some people would say that they couldn’t understand why a woman who just had a baby would not be happy and content. Most women are, but if the stress from the pregnancy and from childbearing were too much for the system, there is a point where the hormones are no longer balanced and the coping mechanisms are undermined.

Serotonin concentrations in the brain of women during pregnancy are kept at a higher level due to higher estrogen levels that slow down the degradation of serotonin. Serotonin is the brain hormone that makes you feel good. Estrogens and progesterone are very high during the pregnancy, but this changes right after the baby’s delivery and during the time of recovery in the first few days and weeks. Studies have shown that there was a 15% higher thyroid autoantibody rate in postpartum depression patients when compared to non-depressed postpartum mothers. This was weakly associated with postpartum depression and was responding favorably to thyroid replacement therapy. Progesterone levels were much lower in depressed and nondepressed patients following delivery because with the delivery the placental source of natural progesterone was removed. In a group of patients where progesterone was replaced, no significant improvement of PPD was observed, but they did not explain whether the progesterone replacement was done with bioidentical hormones or synthetic hormones.

Dr. Michael Platt described a case of a postpartum woman who was hypothyroid as well (Ref.2). She responded to hormone replacement with thyroid hormones and progesterone by shedding 60 pounds (she always had a weight problem) over 10 months changing from a size 20 to a size 4. She was able to wean herself off the anti-depressants. In breast feeding women this could be a significant difference as women on bioidentical progesterone can breast feed and will positively influence their breast fed child’s brain development (brain cells have a lot of progesterone receptors, which are stimulated by progesterone).

A recent Canadian study involving pregnant women and women after delivery of their babies showed that there was a significant drop of progesterone levels in saliva samples for several weeks, particularly with breast feeding. The authors explained that the lack of ovulation with a lack of progesterone synthesis in the ovaries was responsible for this. It takes several weeks for most women to regain regular menstrual cycles. It would follow from this that there is room for bioidentical progesterone replacement in the first few months of the postpartum period until the ovaries have resumed their normal cyclical hormone activity.

Conventional treatment for postpartum depression

With baby blues the symptoms are much less severe (compared to PPD) and are starting 2 to 3 days after childbirth, resolving spontaneously within 10 days after delivery. PPD occurs within 3 months following delivery and responds to treatment with antidepressants and psychotherapy such as cognitive behavioral therapy.  Breast feeding needs to be stopped, as it is known that metabolites of the antidepressants end up in breast milk. Typically, a less toxic antidepressant is used like paroxetine (Paxil), otherwise citalopram (Celexa), and fluoxetine (Prozac). In the rare cases where PPD is so severe that psychotic symptoms are present (postpartum psychosis) hospitalization is mandatory (Ref.3). Some of these cases may require electroconvulsive therapy (ECT) and/or lithium treatment for mood stabilization. Thyroid hormone therapy has also shown a beneficial effect in treating antidepressant-resistant cases of PPD (Ref.4).

Alternative treatment of postpartum depression

Although review texts of the treatment of PPD mention that estrogen replacement in postnatal women with PPD was beneficial, there is a warning that this could cause blood clots and anticoagulant measures would have to be combined with this to prevent deep vein thrombosis; suggestions for progesterone replacement were mentioned, which is a treatment modality where blood clots are no danger, but formal trials have not been done, so it is being ignored by most medical professionals. Here is forum of women who have taken postpartum progesterone with positive effects.

Dr. Katherina Dalton published a trial involving 30 PPD patients with a positive response rate of 95% when treated with natural progesterone.

Before treatment patients were suffering from an average of 7.57 symptoms, after the treatment only 2.1 symptoms remained. (Figures with details regarding this study can be found under the above link).

There are many uncontrolled observations like this where natural progesterone creams are incorporated into a holistic approach to treating PPD. Dr. Mercola describes here how useful natural progesterone therapy can be. He also cautions that it should be taken cyclically to mimic nature’s biorhythm to allow progesterone receptors to recover in between treatments.

There are many websites that have useful information about natural progesterone cream treatment for PPD, such as this.

Conclusion

It is common sense that a woman may need natural progesterone following a delivery, because she just got rid of her placenta, which was a virtual progesterone factory protecting her body and the baby’s brain all throughout the pregnancy. Even if a woman decides to only use natural progesterone in a cyclical fashion for 3 to 6 months, the majority of women would not experience the baby blues or PPD. When regular menstrual cycles have been re established, the patient’s own ovarian progesterone production has resumed and progesterone cream is no longer needed until after the birth of  the next child or at the arrival of menopause. Medicine is full of examples where common sense was applied for effective treatment options despite missing randomized studies.

Natural progesterone treatment of PPD is one such example, where intuitively it was tried and it worked in many patients. Whether or not a randomized trial has been done does not concern the progesterone receptors (they just do not like the synthetic versions of progesterone, as they block the receptors leading to progesterone deficiency!).  Natural progesterone treatment can also be combined with traditional treatments of PPD.

More information on postpartum depression: http://nethealthbook.com/mental-illness-mental-disorders/mood-disorders/postpartum-depression/

References

1.Teri Pearlstein, MD, Margaret Howard, PhD, Amy Salisbury, PhD and Caron Zlotnick, PhD: “Postpartum depression” : American Journal of Obstetrics and Gynecology – Volume 200, Issue 4 (April 2009)

2. Dr. Michael E. Platt: The Miracle of Bio-Identical Hormones; 2nd edition, © 2007 Clancy Lane Publishing, Rancho Mirage, Ca/USA (p.53-55).

3. Bope & Kellerman: Conn’s Current Therapy 2013, 1st ed.© 2012 Saunders

4. Jacobson: Psychiatric Secrets, 2nd ed. © 2001 Hanley and Belfus

Last edited Nov. 7, 2014