Abstract

The incidence and prevalence of anxiety and depression is increasing with time and more number of patients are reporting for consultation for the same. Still a large group of patients due to inhibition and social stigma associated with anxiety and depressive illness, either do not report or get delayed consultation when severity of symptoms has increased, then they seek consultation from the specialist. One more important aspect is that many patients of anxiety and depression report with functional complaints pertaining to various systems of body like headache, pain abdomen, Irritable bowel syndrome, anorexia, breathlessness and chest pain etc. but when you in depth analyze and on regularly following these patients, it is concluded that these are not organic complaints but functional. In many specialties and super-specialties, even this group reaches to 30% of total patients seen being thought to be having problem related to that speciality or super-speciality. Many of above patients of Anxiety and Depression has prominent problem of insomnia for which sedatives are added but in view of their interaction with antidepressant and antiaxiety drugs, there can occur serious side effects, which can even be life threatening. Hence, a rationale use and awareness of all these interactions is must for treating physicians.

Keywords: Zolpidem; Citaloparam; Clonazepam; Depression; Anxiety; Sedative –hypnotic; Insomnia.

Citation: Lakshay S, Malhotra P, Vohra M, Sharma V, Lakra S. Combined use of sedatives and antidepressant mandates rational approach. J Clin Images Med Case Rep. 2023; 4(2): 2295.

Introduction

Zolpidem is used to treat insomnia (difficulty falling sleep or staying sleep). It belongs to a class of medications called sedative-hypnotics and works by slowing activity in brain to allow sleep. Zolpidem may cause serious or possibly life threatening sleep behaviors. Some people who took it got out of bed and drove their cars, prepared and ate food, had sex, made phone calls, sleep-walked, or were involved in other activities while not fully awake [1]. After they woke up, these people were unable to remember what they had done. It can also cause behavioral and mental health changes like aggressiveness, strange or unusually outgoing behavior, hallucinations, memory problems, difficulty in concentrating, anxiety, slowed speech or movements, new or worsening depression, drugged feeling, insomnia and confusion. Other reported side effects include nausea, constipation, diarrhea, gas, heartburn, stuffy nose, nasal irritation, dry mouth and throat, redness of tongue & eyes, muscle aches, joint or neck pain, weight gain or loss and heavy menstrual bleeding. It is normally adviced that Zolpidem should not be added to another sleeping pill and not to be used in alcoholics and pregnant females. It is also be to avoided above 65 years of age, as it is not thought to be safe and other alternatives are available.

Escitalopram, the S-enantiomer of Citaloparam, is a highly selective serotonin reuptake inhibitorwhich increases the level of serotonin, a chemical messenger that improves mood. It has been shown to be an effective and well-tolerated treatment for depression and anxiety disorders in different placebo controlled trials [2-5]. Escitalopram has been shown to be effective for treating Major Depression (MDD); However, research is lacking regarding its effect on treating MDD-related sleep impairments [6]. Clonazepam is a benzodiazepine which increases the action of GABA, a chemical messenger that suppresses the abnormal activity the nerve cells in the brain. The Escitalopram and Clonazepam combination can cause nausea, headache, dizziness, confusion, drowsiness, fatigue, sleeping problems, breathlessness, poor coordination of movements, difficulty in concentrating, increased salivation, frequent urination, stomach upset, decreased libido, anorgasmia, delayed ejaculation and memory problems. The drugs which should not be taken along with Clonazepam include Zolpidem, antihistaminic such as diphenhydramine, narcotic pain medication such as morphine, oxycodone & hydrocodone and opiod cough medications like codeine cough syrup. The use of Zolpidem together with Escitalopram may increase side effects such as dizziness, drowsiness, confusion and difficulty in concentrating. The Escitalopram may cause Zolpidem to stay in system longer hence potentiating its side effects.

Case 1

A Fourty seven year old female, hypertensive, was being treated for idiopathic depression intermittently for last three years was being treated with S-Citaloparam 10 mg and Clonazepam 0.5 mg combination but in last episode due to insomnia, in addition to above drug combination, tablet Zolpidem 10 mg was added. Immediately after addition of this drug, patient after taking both these drugs at bed time, started having excessive yawning, myalgias, increased thirst & urinary frequency and there was a lot difficulty in induction of sleep cycle. After 1-2 hours, patient went became over sedated and in state of delirium, having increased hunger for which she used to eat in midnight, whatever was available in kitchen. The husband told that, even sometimes she use to perform sex with her in that stage but was not able to recall the same after waking up in the morning. Sometimes, even due to difficulty in induction of sleep cycle, patient use to add tablet Alprazolam. 25 mg in night but for partial relief. When these symptoms persisted every night, then on consultation with psychiatrist, the tablet S-Citaloparam & Clonazepam combination was shifted in morning after breakfast and alone Tablet Zolpidem 10 mg was used at night time. It lead to reversal of symptoms of increased thirst, hunger & urination, myalgias and delirious behavior and now she used to remember all the happenings in the night.

Case 2

A Eighty Six year old male, on antihypertensive (Telmesartan 80 mg & Amlodipine 5 mg) for last Fourty years, on oral hypoglycemic (Glimiperide 6 mg & Pioglitazone 30 mg) for last ten years and treatment with Silodosin 8 mg for features of Prostates. He had history of idiopathic depression which used to get precipitated on change of weather like summer to winter and vice-versa. He was treated intermittently for same in last fifteen years with S-Citaloparam 10 mg and Clonazepam 0.5 mg combination. He started having insomnia, in addition to above drug combination, tablet Zolpidem 10 mg was added. He started having increased thirst & frequency of urine which was attributed to increased severity of Prostate and Silodosin dose was increased and his water intake after 8 PM in night was restricted but not for any relief. He started having increased hunger in night, despite having proper meal in night. It was thought to be due to suspected hypoglycemia but repeated blood sugar monitoring during episodes of increased hunger in night time were normal or increased. He was also having increased yawning which was thought to be behavioral and myalgia which was attributed to his old cervical problem. Later on severity of symptoms increased and patient started eating anything available in kitchen like old sweets, table sugar etc in night. He used to make tea repeatedly in night of his own and drank the same. During, these episodes in night, he used to be in delirious state, sometimes used to fell from bed or sleep half on bed and half on floor but was totally unaware of all these happenings, upon waking up in the morning, on being discussed by rest of family members who used to visualize all this behavior personally that too multiple times. On consultation with Psychiatrist, immediately Zolpidem was stopped and in place of that Alprazolam. 25 mg was added to S-Citaloparam & Clonazepam combination. This led to marked reduction in symptoms of myalgia, yawning, increased thirst, hunger and frequency of urine. His delirious state episodes in night also vanished and gave solace to all the family members.

Conclusion

The patients are best teacher for doctor who is lucky to gain experience on them and not only getting paid for it but also earn name and stature also. Every treating doctor should have knowledge of drug interactions and should remain vigilant for the same, as timely detection and intervention can be life saving. In our case, the old man was at full risk of getting hurted by falling from bed and femur neck fracture at this age are most common which are attributed to fall. The other important aspect which came out from female patient, was that combination S-Citaloparam & Clonazepam and Zolpidem can lead to delirious stage and patient even become unaware of sexual relations, thus the same can be misused sexual intoxicants.

Declarations

Conflict of interests: The authors declare that they have no conflict of interests.

Financial support: The authors declare that no financial support was taken for above study.

References

1. US Food and Drug Administration (FDA). FDA adds boxed warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines. FDA Drug Safety Communication, 2019. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia (Accessed on May 08, 2019).
2. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI Escitalopram in depressed outpatients. J. Clin. Psychiatry. 2002; 63: 331–336
3. Colonna L, Reines EH, Andersen HF. A randomized, double-blind, 24- week study of Escitalopram (10 mg/day) versus Citaloparam (20 mg/day) in primary care patients with major depressive patients with major depressive disorder. Curr Med Res Opin. 2005; 21: 1659–1668.
4. Lepola UM, Loft H, Reines EH. Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2003; 18: 211–217.
5. Wade A, Lemming OM, Hedegaard KB. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002; 17: 95–102.
6. Wataru Yamadera, Michiaki Morita, Satoshi Sakamoto Kazuhiko Nakayama. Comparison of Escitalopram alone and combined with Zolpidem in treating major depression and related sleep impairments. Sleep and Biological Rythms. 2016; 14.