Use of Antidepressants in Treatment of Comorbid Diabetes Mellitus and Depression as Well as in Diabetic Neuropathy

After a brief review of epidemiology, the focus is on biochemistry of diabetes. Animal and human studies are reviewed in terms of the impact of alterations in catecholamines and serotonin (5-hydroxytryptamine, 5HT) on glucose utilization. Then, the implications of these experimental results for the choice of antidepressant in comorbid diabetes mellitus and depression as well as in diabetic neuropathy are discussed. Results of clinical investigations are then reviewed in terms of the above hypotheses. An Index Medicus Search for the past 10 years was supplemented by references from previous related reviews of the topic as well as by pending results, where available, not previously published. The range of prevalence of depression in diabetic patients has been 8–27%, depending on study criteria and procedures. An increase of catecholamines appears to increase glucose while both reducing insulin release and reducing sensitivity to insulin that is available. In contrast, increases in serotonergic function by increased precursor, increased release, or blocked metabolism and blocked reuptake in contrast seem to increase sensitivity to insulin and reduce plasma glucose. There have been six studies of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), at a dose of 60 mg/day pursued up to 12 months that have demonstrated that medication's usefulness in diabetic patients, with reductions in weight (to 9.3 kg), in FPG (to 45 mg%), and in HbA1c (to 2.5%). In studies in comorbid diabetes mellitus and depression, nortriptyline, a norepinephrine reuptake inhibitor that produces increased synaptic catechols, has led to worsening of indices of glucose control. However, fluoxetine and sertraline, both selective serotonin reuptake inhibitors, in the same patient group, have produced results consistent with reductions in glucose levels. In diabetic neuropathy, perhaps due to the fact that catecholamines and serotonin may both be implicated in pain pathways, dual-action antidepressants appear more effective at lower doses than do specific serotonergic agents. The tricyclic antidepressants (TCA) (66.7%) have had success in double-blind studies, particularly imipramine, with a 81% response rate. Yet, there are positive reports concerning the SSRIs (paroxetine, citalopram, sertraline), as well as nefazodone, that focus on serotonin selectivity. Conclusions: In comorbid diabetes mellitus and depression, most evidence supports the use of fluoxetine in control of glucose handling. Other characteristics in terms dosing, drug interactions, cognition, and sleep make sertraline an attractive alternative agent. In diabetic neuropathy without depression, the best choices among non-TCAs may include sertraline, citalopram, and perhaps, venlafaxine, since the TCAs appear to increase cravings and increase FBG levels.     

2012～2014年我院抗抑郁药物应用分析

目的了解我院2012~2014年抗抑郁药物的临床应用情况。方法对抗抑郁药物的品种、销售金额、DDDs、DDC等进行了统计分析。结果抗抑郁药物的使用总金额逐年增长,平均年增长率为80.99%。3年来,选择性5-HT再摄取抑制剂(SSRIs)销售金额均居各亚类第1位,占比例均达90%以上。结论我院抗抑郁药物临床应用广泛,使用量与金额均呈快速增长趋势。     

The art of prescribing. Antidepressants in late-life depression: prescribing principles

QUESTION: Ms. Antai-Otong, I am a psychiatric nurse practitioner currently employed in a large primary care clinic. My greatest challenge with older adults suspected of being depressed is their hesitancy to admit they are depressed or unwillingness to take antidepressants. I have started some of these patients on antidepressants and had mixed results. Please provide some guidelines for treating depression in older adults with coexisting medical conditions. ANSWER: Depression is a common companion of chronic medical illnesses and frequently goes unrecognized and untreated, resulting in high morbidity and mortality. Depression is unrecognized and underdiagnosed in approximately 16% of older patients seen in primary care settings (Unutzer, 2002). Typically, older adults deny being depressed, minimize symptom severity, fail to recognize common subjective experiences, such as anhedonia, fatigue, and concentration difficulties associated with this disorder, and hesitate to accept their illness due to social stigma and effects of stoicism. Cultural and generational influences also impact how older adults perceive mental health services. Due to the growing number of individuals 65 and older with coexisting medical and psychiatric conditions, particularly depression, seeking health care in vast practice settings, advanced practice psychiatric nurses must collaborate with primary care providers and develop holistic care that addresses coexisting chronic medical and psychiatric conditions.     

从医疗安全角度谈三环类抗抑郁药中毒

目的:探讨三环类抗抑郁药中毒治疗过程中的医疗安全问题.方法:回顾分析三环类抗抑郁药中毒患者19例的病历资料.采用连续心电监测,碱化血液治疗,气管插管机械通气保护下洗胃,及时有效地控制心律失常,床旁血液净化治疗等方法.结果:治愈17例,死亡2例,无医疗纠纷发生.结论:三环类抗抑郁药中毒不同于一般镇静安眠药中毒,存在医疗安全隐患.认真履行预见告知义务和成功有效的治疗可防范医疗纠纷的发生.     

Quelques aspects pharmacologiques sur un modèle de douleur neuropathique périphérique chez le rat

Résumé  Quelques aspects pharmacologiques obtenus sur un modèle animal de neuropathie périphérique obtenu par constriction partielle du nerf sciatique sont présentées ici. Les antidépresseurs réduisent les anomalies du comportement nociceptif de ces animaux, et ceci à très faible dose. La sympathectomie chimique, ou chirurgicale, prévient ou réduit la réactivité des animaux aux stimulations thermiques chaudes (45°C) ou froides (10°C). La clonidine, agoniste α-2 noradrenergique, a une action antinociceptive prononcée sur la réactivité des animaux aux stimulations thermiques, mais un effet modéré sur leur réactivité aux stimulations mécaniques (seuil de vocalisation induite par pression de la patte). Les substances morphiniques sont efficaces à faibles doses sur les réactions comportementales anormales induites par des stimulations mécaniques ou thermiques nociceptives (46°C) mais cependant, ne le sont pas sur les réactions anormales à la plupart des stimulations thermiques (de 10 à 44°C). Des antagonistes de la cholécystokinine ou du récepteur NMDA accroissent ou révèlent l’action antinociceptive de la morphine. La participation d’une composante périphérique dans l’action antinociceptive des substances opio?des administrées par voie systémique, est mise en évidence. L’administration répétée de morphine induit l’apparition de phénomènes de tolérance et dépendance aux opio?des, qui sont prévenus par l’administration simultanée de l’antagoniste des récepteurs B de la cholécystokinine.

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Summary  Some pharmacological aspects obtained in a well-established rat model of painful peripheral unilateral neuropathy (chronic constriction of the common sciatic nerve) are described: acute and chronic injections of tricyclic antidepressant drugs reduced abnormal pain-related behaviour in these animals. Chemical or surgical sympathectomy prevented or reduced thermal (10°C or 45°C) pain-related behaviour. The α-2 adrenoceptor agonist, clonidine had a moderate effect on the abnormal reactions to mechanical stimuli. By contrast, it dramatically attenuated abnormal responses to hot or cold stimuli. Opioid substances produced dose-dependent antinociceptive effects against a mechanical and a noxious hot (46°C) stimulus. In contrast, morphine was ineffective against a non-noxious cold (10°C) and a non-noxious warm (44°C) stimulus. A NMDA or CCK-B receptor antagonist enhanced the antinociceptive action of systemic morphine. A peripheral component in the antinociceptive effect of systemic opioids is revealed. Morphine pretreatment resulted in tolerance to the antinociceptive effects of systemic morphine. Pretreatment with a CCK-B antagonist prevented the development of tolerance to the antinociceptive effect of morphine as well as morphine dependence.

     

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant,in healthy subjects

The effect of food on the pharmacokinetics of BMS-181101, a new anti-depressant under development, was investigated in 12 healthy male volunteers at steady state. Each subject received a 15 mg oral dose of BMS-181101 twice a day (q 12 h) for 11 days and a morning dose of BMS-181101 on day 12. Six subjects were randomly assigned to receive BMS-181101 under fasted conditions from days 1 to 6 and then crossed over to fed conditions from days 7 to 12. The other six subjects received the reverse conditions, fed for days 1–6 and fasted for days 7–12. Serial blood samples were collected up to 12 h on days 6 and 12 following the administration of the morning dose. In addition, trough blood samples were collected on days 4, 5, 10, and 11 prior to the morning dose. Plasma samples were analyzed for intact BMS-181101 using a validated high-performance liquid chromatography method with an electrochemical detector. BMS-181101 was well tolerated both with and without ingestion of food. The statistical evaluation of the C_min values indicated that steady state of BMS-181101 was achieved by the fourth day of dosing regardless of whether the subject was fasted or fed. When BMS-181101 was administered with food, C_max was reduced by about 25% and t_max was prolonged by 1 h. However, AUC_tau, t_1/2, and time to attain steady state of BMS-181101 were not altered by ingestion of food. In summary, BMS-181101 can be given with food without adversely impacting the safety or pharmacokinetic profiles of the drug. © 1997 John Wiley & Sons, Ltd.     

Medication use in patients with restless legs syndrome compared with a control population

Primary restless legs syndrome (RLS) is a sensorimotor disorder causing chronic sleep deprivation in those with moderate to severe symptoms. It has been associated with other medical conditions, such as high blood pressure, depression and attention deficit hyperactive disorder (ADHD). If these conditions are more prevalent for RLS patients, then it would be expected RLS patients would use relatively more of the medications treating these conditions. Current medication use was obtained from 110 RLS patients and 54 age, race and gender-matched local-community controls. Each subject was diagnosed as primary RLS or having no indications for RLS by a clinician board-certified in sleep medicine. The RLS group used more medications than the control group even when medications used for treating RLS were excluded. Significantly more of the RLS patients than controls used anti-depressants, gastro-intestinal (GI) medications and asthma/allergy medications. RLS patients compared with those without RLS are more likely to use medications not related to treating RLS. Moreover they use medications for conditions that have not previously been considered related to RLS, i.e. GI and asthma/allergy conditions.     

A commentary: Measuring the health economics of depression

The perspective of a health economic analysis is vital and this is particularly true in the current debate on the economic analysis of Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). The perspective can be institutional, from central government, region, health commission to GP fundholder, and it can be by cost type: including drug costs alone in the analysis; other direct costs such as GPs' and counselling time; and indirect costs such as loss of earnings due to depression. Economic analysts, who focus on drug costs alone tend to favour TCAs over SSRIs. Those who cast their cost net wider tend to favour SSRIs over TCAs. Future research should concentrate on the ‘invisible costs’ that exist in the prescribing process; and on quality of life and health outcomes to establish treatment cost/successful outcome. This could form an intergral part in the development of future cost effective guidelines for depression.     

Prenatal treatment with clomipramine has an anxiolytic profile in the adolescent rat

The tricyclic anti-depressant clomipramine (3, 10 or 30 mg/kg/day) was administered to pregnant rats between days 8 and 21 of gestation. Male pups were cross-fostered at birth and raised in litters of eight. After weaning (postnatal day 21) the offspring were raised in an enriched environment and were then subjected to a variety of behavioral tests, lasting through adolescence (days 35 to 42), and repeated in adulthood (day 70 onwards). As has been found when imipramine was administered prenatally, the offspring showed decreased rearing and less exploration; however, the latter was entirely due to more rapid habituation to the test environment. The treatment produced an anxiolytic profile when the adolescents were tested in the Social Interaction test of anxiety. Effects did not persist into adulthood, although it may be that this was the result of repeated testing.