THE NOCTURIA (OR NYCTURIA) IN ELDERLY PERSONS WITHOUT PERIPHERAL URINARY PROBLEMS CAN BE REDUCED OR ABOLISHED WITH AN ANTISTRESS DRUG THERAPY? PRELIMINARY REPORT ON 7 CASES TREATED WITH ANTIDEPRESSANT-ANTISTRESS DRUGS.

Renato COCCHI, a neurologist and a medical psychologist.

(Other cases of nocturia treated by antistress drugs) 

 

Summary.

In seven patients (5 F and 2 M; average age 68 years at first consultation, with 57-79 years range) all suffering from nocturia, it resulted that the nocturia messed by modulating the stress reactions by drugs, when considering as normal null or one awakening every night. In four cases out of seven the sleep had no more breakdowns. The nocturia is a trouble of the elderly, from nighttime parasympathetic overstimulation of brain origin, probably linked to the stress of aging. In its turn it gets out to an increase of the same stress condition, just by altering the sleeping-waking rhythm. By this away it increases the fall frequency, sometimes with traumas, and it induces reduced vitality during the day.

Key words: Elderly, nocturia, stress, nighttime awakening, fall, trauma, vitality, drug therapy.

 

Italian translation.

 Drug modulation of stress reactions

Others.

Stress symptoms

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Recently, following an observation of a physician colleague, my attention kept at a curious fact. His elderly wife with depression and tinnitus, during the antidepressant-antistress therapy I prescribed, missed the need to get up often every night, to go to the bathroom to urinate (See the case no. 5).

A specific question to other elderly persons who recently came to checkups between November and December 2004, led to track down other six similar cases

 

Introduction.

The nocturia (or, the nycturia) is the excessive need to urinate during the night (at least two waking up again for this purpose), in particular in elderly people, but it does not occur in same age persons (Weiss and Blaivas, 2000).

In 2004 this symptom had a particular investigation in off family situations, rest houses or hospitals, mainly in relationship to falls and to possible following traumas.

In rest houses for elderly, the residents have a meaningful risk to fall even linked to the nocturia (Hui-Chi, 2004).

 Following a hospital investigation lasting 13 weeks, it appeared that the half the falls went with evacuation needs, and they were more common in patient with over 65 years. The falls from voiding needs have a greater risk to set up subsequent lesions (Hitcho and coll., 2004).

In an investigation lasted three years, the most falls in hospital (73.5%) occurred in hospitalization rooms; Other 20% to the floor between the room and the bath, or in the bath (Von Renteln-Kruse and Krause, 2004).

It follows on that from the 20% to the 50% of the falls in the hospital or in rest houses are due to evacuation needs, mainly to urinate during the night, with risks of even burden traumas.

Various conditions favour these accidents. The need to urinate more of eight times daily and to go quickly to the bathroom for urgency to urinate, during the night, are among first ones. The nocturia has to be added to them, as an awakening for the need to empty the bladder two or more times every night.

Mainly in its nighttime occurrence, this is a problem that we tried to resolve. So, by drugs acting on the bladder detrusor (low dosing tricyclic antidepressants, or oxybutyrine hydrochloride, or tolterodine tratrate or with desmopressin acetate, a synthetic analogous of the natural antidiuretic hormone).

In the case histories here presented, all the patients were still living in their families.

 

Case histories.

1. F, 77 years old at the first examination, suffering from not familiar maniac-depressive disorder, since about 45 years, with onset after delivery. April 2004: I saw her fort the firts time, being in a depressive phase, in treatment with lithium carbonate, fluoxetin and triazolam.

She is waking up 2-3 times every night to go to the bath room to urinate.

She had her last checkup on December 2004: Since eight days she turned back in the maniacal phase.

At the moment she reverted to the euphoria, she was taking a regimen with lithium carbonate 300mg, carbamazepine 200mg, clomipramine 25mg, oxazepam 15 mg, clothiapine 10mg, clonidine 0.075mg, amantadine 50mg.

Since many months she had 0-1 nocturia episodes every night.

2. M, 57 years at the first consultation, he shows results of an ischemic attack in the right half-brain, with paralysis to the left superior limb and paresis of the left inferior limb.

I visited him on July 2003 for continuous pain of the left shoulder, only reducible with analgesic drugs, but not with acupuncture. I hypothesized a thalamic pain. He needs to get up 2-3 times every night to urinate. I prescribed this drug therapy (daily doses, by the oral via): Glutamine 125mg; A-adenosil-l-methionine (SAMe) 100mg; pyridoxine 150mg; carbamazepine 200mg; creatine 2000mg; chlomipramine 20mg; bromazepam 1mg.

The third decade of November 2004: The last checkup. He is taking drug therapy with Amitriptyline + perphenazine 25mg + 2mg; Glutamine 62.5mg; SAMe 100mg; Creatine 2000mg; Carbamazepine 300mg; bromazepam 1mg. At night he sleeps at least six hours and half continuous sleeping. He does not more need to get up to urinate.

3. F, 63 years old at the first consultation, with problems of the eyes, atypical anxious depression. In the first decade of September 2004, she had the first visit when she was taking 2mg lorazepam daily. She was falling asleep late and woke up early, about five in the morning. Every night she woke twice to go in the bathroom. Her initial therapy had glutamine 125mg; pyridoxine 75mg; carbamazepine 100mg; amitriptyline 6mg; lorazepam 0.5mg.

In the first decade of December, she did a checkup after three months of drug therapy, which varied by increasing amitriptyline to 10mg daily. She did not need to get up to urinate during all night.

4. F, 76 years old at the consultation on January 1996, a widow and the mother of the present author, lived alone since 12 years, she met weekly her son and her daughter. She was suffering from of senile depression with relapses 2-3 times every year, because she stopped the drugs when well off. Currently she has gone to live with the daughter, who will take care of the regular taking of the drugs. Her regimen is now amitriptyline 16.50mg + chlordiazepoxide 8.5mg. When she stopped the therapy, she had to get up 4-5 times every night to urinate. In therapy she woke up 1-2 times every night.

The final checkup, on November 2004, did not show any dementia signs. After eight years of drug therapy, currently with glutamine 125mg, amitriptyline 5mg + chlordiazepoxide 5mg, lorazepam 1.25mg, a polyvitaminic compound with mineral salts once for week, she did not have anymore depressive relapses. Since at least 6-7 years she not has any need to get up at night to urinate.

5. F, 66 years old, a wife of a general medicine physician, she at the first consultation in the third decade of September 2004. She is suffering from an intermittent tinnitus, which started five months before. Now she is depressed and anxious, besides poorly convinced in favour of the psychodrugs use. She is taking 0.167mg delorazepam and 150mg pyridoxine, with null results. She has a bad sleep even because she is lifting every half an hour to urinate. The husband, as a physician, checked the amount of the nighttime urine, which came even to 2800ml in total.

I prescribed therapy of glutamine 125mg; pyridoxine 75mg; carbamazepine 100mg; amitriptyline 10mg; delorazepam 0.334mg.

The last checkup occurred in the third decade of December 2004, after 98 days of drug therapy. She much improved the anxiety and the depression, unchanged or slightly diminished the tinnitus. During the preceding checkup, the carbamazepine increased to 200mg. She is sleeping well and does not need to get up at night to urinate.

 6. M, 57 years at the first examination he acted in the second decade of September 2004 for subjective vertigoes, irritability and memory deficits. He has to wake at least three times every night to urinate. Already in therapy with fluoxetin and triazolam and levopropionilcarnitine. I prescribed: Glutamine 125mg; 5-hydroxitriptophano 50mg; pyridoxine 75mg; amitriptyline 6mg; oxazepam 7.5mg.

The second checkup in the second decade of December 2004, with unchanged therapy showed that the nocturia was then 0-1 episode every night.

7. F, of 79 years at the first consultation, asked for senile anxious and reactive depression, with asthenia. She is waking 3-4 times every night to go in bathrom to urinate.

Initial therapy: Glycine 150 [mg] (in Biotassina TM), Vit B1-B6-B12 125mg + 125mg + 0.5mg, amitriptyline + perphenazine 10mg + 2mg, delorazepam 0.5mg.

The second decade of December 2004, the second checkup, after having previously substituted the glycine with the glutamine 250mg, during the first checkup. Now, the nocturia episodes sum 0-1 every night.

 

Tab. 1: Summary of the drugs (daily doses, by the oral via) and results.

Drug

Dosing (mg)

No. of patients

Glutamine

62.75-250

6

Pyridoxine

75-150

4

Carbamazepine

100-300

4

Amitriptyline

6-25

5

Chlomipramine

10-25

2

Perphenazine

2

2

Oxazepam

7.5-15

2

Lorazepam

0.5-1.25

2

Delorazepam

0.334

2

Bromazepam

1 mg

1

Chlordiazepoxide

5

1

Lithium carbonate

300

1

Amantadine

50

1

Clothiapine

10

1

Clonidine

0.075

1

S-adenosil-l-methionine

100

1

Creatine

2000

1

5-hydroxi-triptophan

50

1

Glycine (in Biotassina (R)

150

1

Vit. B1+B6+B12

125+125+0.5

1

   

Total of drugs

20 // Average per patient: 5.7

  

Results on the nocturia

Disappearance

7 out of 7 = 100%

Nightime awakenings

Disappearance

4 out of 7 = 57.14 %

Nocturia is not more present in seven cases out seven and in four cases out of seven there is not anymore need to get up to urinate. The drug therapy was individually tailored.

 

Discussion.

Already from the title it would seem to exclude the so-called "overactive bladder" as a peripheral urinary problem, not because there is not an overactive bladder, but because, as for me, it is not a primary problem. Even it would be the result of a fluctuating parasympathetic outflow coming from the brain, as stress reaction. For the nighttime bedwetting the brain implication is not a new datum (Von Gontard and coll., 2001), but nighttime bedwetting and nocturia are not the same urinary trouble.

No patient, of the rest, did mention a similar diagnosis during the first consultation.

In the second place, this result had not looked for, but it was incidentally reported for first time by a physician colleague, as particularly sensitized to his wife trouble. Then it had systematic investigation in patients who came to the checkup between November and December 2004. This is the reason of the anecdotal report on these first seven cases.

The datum, which five cases out of seven are women, by now it doesn't want to say anything. It doesn't allow to affirm that it means a specific prevalence of this symptom in the female gender. It could be simply creditable to the greater easiness of the women, even elderly ones, to have depressive pathology. Otherwise, it could even be truly casual.

In all these seven patients I prescribed at least a tricyclic antidepressant, sometimes by replacing the antidepressant previously taken. The peripheral anticholinergic (antispasmodic) action of the tricyclic antidepressant may have contributed to the improved control on the voiding of the bladder, by an action on the detrusor muscle. Personally, for these cases, I am not sure of the efficacy of such an action, as it is also known from the literature on this matter (Pontari, 1997).

Other used antispasmodics include the oxibutynine as an inhibitor of the acetylcholine and the tolterodine tartrate, as an antagonist of the acetylcholinergic muscarinic receptor (Anderson, 2002). Any of them have been taken by these patients.

Different the action elicited by the desmopressin acetate, a synthetic analogue of the natural antidiuretic hormone, on the nocturia. By reducing the urinary outflow, it reduces the bladder filling and the emptying stimulus (Asplund and coll., 1999; Mattiasson and coll., 2002; Lose et al., 2003, Rembratt, Andersson and Norgaard, 2003). In this way it allows longer sleeping times and it reduces the stress from the broken sleep, which strikes again on the life and on the daily activity (Kobelt, Borgstrom, and Mattiasson, 2003). None of these patients had used the desmopressin acetate.

Since I acted on the depression, with the tricyclics, the 5-hydroxitriptophan and the SAMe, and on the stress reactions with the benzodiazepines, the glutamine, the pyridoxine and the carbamazepine, the result on the stress was surely wider. Moreover, it found, as an effect not looked for, the reduction within the limits of the normalcy, or the disappearance of the awakenings for the nocturia.

 

Conclusions.

The nocturia, as awakening out by the need to urinate, is a trouble of the elderly, probably linked to stress from aging. In its turn, it drives to an increase of the stress condition, by making worse the sleeping-waking rhythm. By this way it increases the falling frequency, even with damage, and less vitality during the day.

In the seven cases here reported we saw that by modulating with drugs the stress reactions, the nocturia is missing, considering as normal a nighttime awakening. In four cases out seven no nighttime awakenings persisted.

 

 (Other cases of nocturia treated by antistress drugs) 

 

References.

Andersson, K.E. The pharmacological treatment of nocturia. BJU Int., 2002, 90 Suppl 3: 25-27.

Asplund R, , Sundberg B, Bengtsson P. Oral desmopressin for nocturnal polyuria in elderly subjects: a double-blind, placebo-controlled randomized exploratory study. BJU Int 1999, 83: 591-595.

Hitcho EB, Krauss MJ, Birge S, Claiborne Dunagan W, Fischer I, Johnson S, Nast PA, Costantinou E, Fraser VJ. Characteristics and circumstances of falls in a hospital setting: a prospective study. Journal of General Internal Medicine, 2004, 19::732-739.

Hui-Chi H. A checklist for assessing the risk of falls among the elderly. Journal of Nursing Research; 2004,12:131-142.

Kobelt G, Borgstrom F, Mattiasson A. Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia. BJU Int., 2003 91: 190-195.

Lose G, Lalos O, Freeman RM, van Kerrebroeck P and The Nocturia Study Group. Efficacy of desmopressin (Minirino(r)) in the treatment of nocturia. A double-blind placebo-controlled study in women. Am J Obstet Gynecol., 2003, 189: 1106-1113.

Mattiasson A, Abrams P, Van Kerrebroeck P, Walter S, Weiss J. Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men. BJU Int. 2002, 89: 855-862.

Pontari, M. Interstitial Cystitis Update. Infect Urol 1997,10:75-79.

Rembratt A, Andersson K-E, Norgaard JP. Desmopressin in elderly patients with nocturia: short-term safety and effects on urine output, sleep and voiding Patterns. BJU Int., 2003, 91: 642-646.

Von Gontard A, Schmelzer D, Seifen S, Pukrop R. Central nervous system involvement in nocturnal enuresis: evidence of general neuromotor delay and specific brainstem dysfunction. J Urol., 2001, 166: 2448-2451.

Von Renteln-Kruse W, Krause T. .Fall events in geriatric hospital in-patients. Results of prospective recording over a 3 year period. Gerontology and Geriatrics. 2004, 3: :9-14.

Weiss JP, Blaivas JG. Nocturia. J Urol., 2000, 163: 5-12.

 

 Posted on Internet on 24 December 2004. Copyright by Renato Cocchi, 2004.

 

Author's address: Dr Renato COCCHI, via Rabbeno,3

42100 Reggio Emilia

renatococchi@libero.it

 

Italian translation.

 Drug modulation of stress reactions

Others

Stress symptoms

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