Hypogonadism in patients treated with intrathecal morphine

OBJECTIVE: The objective of this study was to investigate the hypothalamic-pituitary-gonadal response to intrathecal opioids. PATIENTS: Thirty patients receiving intrathecal morphine for chronic nonmalignant pain were studied for clinical and biochemical evidence of hypogonadism. Ten men and 10 postmenopausal women with chronic pain of similar duration but who were not receiving any form of opioid therapy acted as control subjects. RESULTS: Men and both premenopausal and postmenopausal women had evidence of hypogonadism with low levels of serum testosterone or estrogen coupled with low levels of pituitary gonadotrophins. Control subjects had hormone levels in the expected range for their sex and age. Two men demonstrated recovery after ceasing intrathecal opioid therapy. CONCLUSIONS: Hypogonadotrophic hypogonadism is a common complication of intrathecal opioid therapy in both men and women.     

Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain.

Hypogonadotrophic hypogonadism is characteristically induced in men by intrathecal, transdermal, or sustained-action opioids. Although women receiving intrathecal opioids have similar changes, often accompanied by amenorrhea, hypogonadotrophic hypogonadism has not been documented in women receiving sustained-action, transdermal, or oral opioids. Dehydroepiandrosterone sulfate deficiency, indicating adrenal inhibition, is present in most men and women chronically consuming sustained-action oral or transdermal opioids. We recorded menstrual histories and measured gonadotrophin, androgen, and estradiol levels in 47 women ages 30 to 75 years who were consuming sustained-action oral or transdermal opioids for control of nonmalignant pain and in 68 non-opioid-consuming control subjects. Testosterone, estradiol, and dehydroepiandrosterone sulfate values were 48% to 57% lower in opioid-consuming women with intact ovarian tissue than in control subjects (P < .01-.05). Luteinizing hormone and follicle-stimulating hormone values averaged 30% lower in premenopausal and 70% lower in postmenopausal opioid consumers (P < .001). Among oophorectomized women not consuming estrogen, free testosterone levels were 39% lower in opioid consumers (P < .05), indicating impaired adrenal androgen production. Additional lowering of free testosterone levels was associated independently with oral estrogen replacement and low body mass index. Menses had often ceased soon after beginning sustained-action opioid therapy. Our observations document hypogonadotrophic hypogonadism plus decreased adrenal androgen production in most women consuming sustained-action oral or transdermal opioids. PERSPECTIVE: These observations demonstrate profound inhibition of ovarian sex hormone and adrenal androgen production among women chronically consuming sustained-action opioids. Related consequences include altered menstrual flow, probable reduced fertility, and possible contributions to opioid-associated depression, osteoporosis, and hyperalgesia. Measurements of bone density, estradiol, and free testosterone may guide appropriate therapy.     

Intrathecal Drug Administration in Chronic Pain Syndromes

Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long‐term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo‐controlled trials. A randomized study showed this treatment option to be effective over a short follow‐up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drug administration in patients suffering from cancer‐related pain is more compelling than that of chronic noncancer pain.     

Long-term intrathecal morphine influence on major compounds of the endocrine system in elderly population

BackgroundThe influence of long-term opioid administration on hormonal levels is not well characterized in the literature. We previously showed that intrathecal opioid therapy significantly influences the homeostasis of immune and endocrine systems. Other authors confirmed that exogenous and endogenous opioids induce this effect. They have a cytokine-like behavior and may function as neurotransmitters, neuromodulators or hormones, as concerning their synthesis, storage and release.AimsTo assess the effects of morphine long-term intrathecal administration on serum levels of Gonadal, Thyroidal and Adrenal axis hormones in an elderly population affected by chronic pain; to assess the correlation between hormone levels and morphine dosage.MethodsPatients suffering from chronic non-cancer pain with or without intrathecal drug delivery system were studied and hormonal levels were monitored, using an immunoradiometric assay kit.ResultsThe long-term administration of intrathecal morphine influenced part of the endocrine system, in particular, there was a reduction of FSH and LH and an increment of GH serum levels; this effect was morphine dose dependent.ConclusionLong-term intrathecal opioid administration influenced FSH, LH and GH serum levels. Data on this issue are inadequately described in the literature. The finding of endocrine effects of opioid therapy, nonetheless, cannot be ignored, as it may have clinical relevance in both elderly and young population. We believe that during long intrathecal pain treatments with morphine, clinicians should be aware of both immediate and later opioids side effects, and in particular, they should monitor immune and endocrine changes.     

Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment.     

Intrathekale Opiattherapie bei chronischen Schmerzsyndromen benigner Ätiologie über implantierbare Medikamentenpumpen

The use of implantable systems for intrathecal administration of opioids in chronic pain of non-malignant origin is a controversial subject. Opioid therapy is reserved mainly for pain patients with malignant disease and reduced life-expectancy. The main reasons for this restricted range of indications of chronic subarachnoid administration of opioids are fear of addiction and the build-up of tolerance. During July 1988 and April 1990 we treated 60 patients suffering from pain of non-malignant origin with continuous opioid infusion by implanted pumps. Wishing to find whether opiates can relieve deafferentation pain, we subdivided the different pain syndromes into three groups according to their pathophysiology: nociceptive, neurogenic/neuropathic, and deafferentation pain. After a follow-up period of 11.5+/-7.1 months 47 patients were evaluated. Pain intensity according to the visual analogue scale was reduced in a mean of 79.4% of the patients. Activity level and mood scores as pain-associated parameters were both significantly increased after therapy. Analysis of the McGill Pain Questionnaire reveals that the improved quality of life is attributable to a reduction of affective pain perception more than to sensory discrimination. The best results in terms of pain reduction (82.5%) were obtained in the group of patients with deafferentation pain. This is in contrast to reports in the literature. It seems that neuropathic and deafferentation pain syndroms are susceptible to intrathecal opioids. The initial daily average dose of morphine was 2.6 mg/day, increasing to 6.1 mg/day after 25 months without the development of major tachyphylaxis. the administration of intrathecal opioids by means of implantable systems is justified in carefully selected patients with chronic non-malignant pain. This method should be applied in preference to destructive neurosurgical treatments.     

Hypogonadism in men consuming sustained-action oral opioids.

Naturally occurring opiates (endorphins) diminish testosterone levels by inhibiting both hypothalamic gonadotrophin releasing hormone production and testicular testosterone synthesis. Heroin addicts treated with a single daily dose of methadone and nonaddicts receiving continuous intrathecal opioids quickly develop low luteinizing hormone and total testosterone levels. A similar pattern was sought in men consuming commonly prescribed oral opioids. Free testosterone (FT), total testosterone (TT), estradiol (E(2)), dihydrotestosterone (DHT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in 54 community-dwelling outpatient men consuming oral sustained-action dosage forms of opioids several times daily for control of nonmalignant pain. Hormone levels were related to the opioid consumed, dosage and dosage form, nonopioid medication use, and several personal characteristics and were compared with the hormone analyses of 27 similar men consuming no opioids. Hormone levels averaged much lower in opioid users than in control subjects in a dose-related pattern (P < .0001 for all comparisons). FT, TT, and E(2) levels were subnormal in 56%, 74%, and 74%, respectively, of opioid consumers. Forty-eight men (89%) exhibited subnormal levels of either FT or E(2). Either TT or E(2) level was subnormal in all 28 men consuming the equivalent of 100 mg of methadone daily and in 19 of 26 (73%) consuming smaller opioid doses. Eighty-seven percent (39 of 45) of opioid-ingesting men who reported normal erectile function before opioid use reported severe erectile dysfunction or diminished libido after beginning their opioid therapy. Commonly prescribed opioids in sustained-action dosage forms usually produce subnormal sex hormone levels, which may contribute to a diminished quality of life for many patients with painful chronic illness.     

The use of long-acting opioids in chronic pain management

The consensus statement from the American Pain Society and American Academy of Pain Medicine states that the undertreatment of pain is unjustified [6]. It has been suggested that opioid therapy can be used effectively to treat noncancer pain in a subset of patients [26], and this is becoming more acceptable [3]. Providing sustained analgesia is an important aspect of therapy, and medications should be administered on an around-the-clock basis, because regular administration of doses maintains a constant level of drug in the body and helps prevent recurrence of pain. Ideal treatment for persistent pain is a long-acting opioid administered around the clock to prevent baseline pain, with the use of short-acting opioids as supplemental agents for breakthrough pain. Controlled-release formulations can lessen the inconvenience associated with around-the-clock administration of short-acting opioids. Sustained analgesia also can be achieved with transdermal fentanyl, which combines a strong opioid with a 72-hour release profile and the benefits of a parenteral route, avoiding first-pass metabolism. Controlled-release formulations of morphine and oxycodone are available in the United States, and hydromorphone preparations are being reviewed for approval. Clinical experience with these formulations and transdermal fentanyl indicates that these agents are equally effective in controlling pain. Studies have demonstrated improved quality of life with the transdermal route and with controlled-release morphine and oxycodone. Because of patch reapplication every 72 hours, the transdermal route also enhances compliance. Use of an opioid without the need for oral or intravenous administration and the opportunity to improve compliance are among the advantages of the transdermal route in clinical practice. The nurse has an important role in the management of patients receiving long-acting opioids for chronic noncancer pain, Facilitation of the conversion from short-acting to long-acting opioids may be the initial step. Individualization of therapy to determine which route and product best suits the patient's needs and lifestyle can be accomplished through a comprehensive nursing assessment. Titration of dose along with institution of a short-acting opioid for break-through pain may require frequent interventions that a nurse familiar with the patient can provide. Prevention and management of opioid-related adverse events are essential for effective opioid therapy. Providing patient and family education regarding administration, monitoring, and management of opioid therapy is an important nursing role. Lastly, documentation of pain level, functional status, and opioid-related adverse events is required for each contact with the patient, to make this information available to all who assist in the management of the patient's pain. Chronic noncancer pain is an experience that affects all aspects of a patient's life. Effective pain management with long-acting opioids may help the patient to focus on the positive aspects of life, decreasing the focus on pain.     

Outcome of intrathecal opioids in chronic non-cancer pain

Eighty-eight patients (58 women and 30 men; mean age 53.4 years) with chronic non-cancer pain present on average for 9.8 years were evaluated following treatment with intrathecal opioids for an average duration of 36.2 months. Outcome measures were global pain relief, physical activity levels, medication consumption, work status, intrathecal opioid side-effects, proportion of patients who ceased therapy and patient satisfaction. The most common diagnosis in this group was lumbar spinal or radicular pain after failed spinal surgery (n= 55, 63%). At the time of follow-up, mean pain relief was 60% with 74% of patients (36 of 49) reporting increased activity levels. Oral medication intake was significantly reduced (Medication Quantification Scale Score prior to implantation 31.0+/-2.6 and at follow-up 12.7+/-1.4; n= 48; p< 0.0001). These gains were not accompanied by a change in work status (43 of 50 working age patients not working at follow-up). There were frequent reports of opioid side-effects, including sexual dysfunction and menstrual disturbance. Technical complications occurred with the drug administration device, most often catheter related, requiring at least one further surgical procedure in 32 patients (40%). Patient satisfaction with intrathecal opioids was high, with 45 of 51 (88%) reporting satisfaction. Mean intrathecal morphine dose increased from 9.95+/-1.49 mg/day (mean+/-SEM) at 6 months to 15.26+/-2.52 mg/day 36 months after initiation of therapy. Drug administration systems were permanently removed in five patients (6%). Intrathecal opioid therapy appears to have a place in the management of chronic non-cancer pain. Therapy does not seem to be significantly inhibited by the development of tolerance.     

A systematic review of opioid effects on the hypogonadal axis of cancer patients

Purpose

Opioids are the mainstay of analgesic therapy in patients with cancer-related pain. While many of the side effects of opioids are well documented, the effect on the hypogonadal axis is less well understood. The aim of this systematic review is to examine the relationship between opioid therapy and hypogonadism in patients with cancer.

Methods

An electronic search of the following databases was undertaken: MEDLINE, Embase and CINAHL from 1974 to August 2013. To be eligible for inclusion, studies had to meet the following criteria: adult patients (>18 years) with cancer taking any opioid by any route for any duration, gonadal function measured and the relationship between opioid use and gonadal function examined. All potentially eligible papers were reviewed independently and data extracted using a pro forma.

Results

Four studies met the inclusion criteria. Due to the heterogeneous nature of the studies, it was not possible to amalgamate the results. Three studies suggested a relationship between opioid use and hypogonadism in patients with cancer. These studies also suggested this relationship to be dose dependent. There was evidence to suggest that hypogonadism was symptomatic and associated with reduced survival. One study showed no link between opioids and hypogonadism.

Conclusions

Studies conducted have suggested an association between opioids and hypogonadism in patients with cancer. This warrants further investigation. A longitudinal study examining the impact of opioids on the hypogonadal axis would be of interest.     

Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse.PerspectiveCurrently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.     

Hypogonadism and sexual dysfunction in male cancer survivors receiving chronic opioid therapy

The purpose of this study was to determine the prevalence of central hypogonadism and sexual dysfunction in male cancer survivors exposed to chronic high-dose oral opioid therapy. We studied 20 male patients with cancer-related chronic pain who were disease-free for at least one year. All patients consumed at least 200 mg-equivalent of morphine on a daily basis for at least one year. Participants completed the Sexual Desire Inventory questionnaire and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed. Serum testosterone levels were reduced in these patients. The median value was 140 ng/dL (normal 241-827). There was no compensatory increase in FSH and LH. The median FSH level was 3.5 mIU/mL (normal 1.4-18.1). The median LH level was 2.1 mIU/mL (normal 1.5-9.3). The mean dyadic sexual desire score was 23.9+/-15.7 (normal value, 42.8+/-8.9). The mean solitary sexual desire score was 1.3+/-1.9 (normal value, 10.6+/-1.9). Our data suggest that chronic exposure to high-dose oral opioid therapy may result in marked central hypogonadism and sexual dysfunction. Given the increasing use of long-term opioid therapy for chronic pain syndromes, further investigation into these findings is warranted.     

Nociceptin levels in the cerebrospinal fluid of chronic pain patients with or without intrathecal administration of morphine

The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid-like receptor ORL-1 and is thought to be involved in pain transmission and modulation. Human studies have not yet defined its role in pain patients. The aims of this study were 1) to verify the presence of N/OFQ in the cerebrospinal fluid (CSF) of human controls and patients with chronic noncancer pain, including those treated with intrathecally administered morphine, and 2) to determine whether pain or treatment with long-term intrathecal morphine influences its levels. The CSF of 27 patients (nine controls and 18 with chronic noncancer pain, of whom 12 were treated chronically with intrathecally administered morphine and six were opioid na?ve) was analyzed, blindly, with radioimmunoassay methods. N/OFQ was detected in all patients. Mean CSF concentrations were lowest in the morphine-treated group and highest in the untreated chronic pain patients (12.06+/-1.19 and 57.41+/-10.06 fmol/ml, respectively), and the difference between the morphine-treated group and controls was statistically significant (44.72+/-13.56 fmol/ml, P<0.05). The presence of N/OFQ peptide in human CSF may correlate with biological activities that are influenced by different pain states and long-term intrathecal-morphine treatment. Further studies should verify whether the determination of this peptide CSF level may provide information on opioid treatment efficacy and on the presence of opioid tolerance.     

Hormone changes in men with spinal cord injuries.

The steady state profiles of 63 men with traumatic spinal cord injuries (24 quadriplegics and 39 paraplegics; average age of 31.2 +/- 6.8 yr; 18-44 yr) were studied. The average length of post-traumatic period was 6.2 +/- 5.0 yr, ranging from 8 months to 20 yr. It was found that all the subjects had normal serum thyroxine, thyrotropin, cortisol, growth hormone and plasma adrenocorticotropic hormone. Seven cases (11.1%) had low serum triiodothyronine and eight cases (12.7%) had low serum testosterone. On the other hand, 17 cases (27.0%) had hyperprolactinemia; 9 cases (14.3%) had elevated serum testosterone level; 6 cases (9.5%) had elevated serum follicle-stimulating hormone; and 4 cases (6.3%) had elevated serum luteinizing hormone. The level of spinal cord injury, injury period and patient age had no correlation with other serum hormone changes except that quadriplegic subjects had lower serum triiodothyronine than the paraplegic, with a mean of 1.42 +/- 0.30 v 1.70 +/- 0.36 nmol/liter (P < 0.005). Of the eight subjects who had low serum testosterone, none had elevated gonadotropin. There were also eight subjects with elevated follicle-stimulating hormone and/or luteinizing hormone, six of them had normal serum testosterone and two had elevated serum testosterone. This suggested their hypogonadism did not result primarily from classic primary gonadal failure. It could be speculated that other testicular paracrine factors and/or alteration of hypothalamus-pituitary-testicular axis are involved in the pathogenesis of hypogonadism. Further studies in this field will provide information regarding male reproductive physiology and may have impact on fertility enhancement options for men with spinal cord injuries.     

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices.PerspectiveSafe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.     

Stability, compatibility, and safety of intrathecal bupivacaine administered chronically via an implantable delivery system

OBJECTIVE: The only agent approved by the U.S. Food and Drug Administration for chronic intrathecal infusion for the treatment of chronic pain is morphine sulfate. In patients who do not experience adequate relief from intrathecal opioids, bupivacaine is frequently added to increase efficacy. The studies reported here were conducted to demonstrate the stability and compatibility of bupivacaine in a commonly used implantable infusion system and the long-term clinical safety of this therapy. METHODS: A commercially available bupivacaine solution (7.5 mg/ml) was incubated at 37 degrees C for 12 weeks with intact delivery systems and with the individual materials that comprise the fluid pathway. Intermittent samples were collected and analyzed using liquid chromatography. Materials chronically exposed to bupivacaine were analyzed for mechanical integrity. One hundred eight patients treated with intrathecal bupivacaine (average dose: 10 mg/d, range: 2-25 mg/d) and opioids for an average duration of 86 weeks were monitored clinically (patient interviews and neurologic examinations) approximately every 4 weeks. RESULTS: Bupivacaine concentrations remained greater than 96% of the starting material after chronic exposure to the delivery system materials or the intact pump-catheter systems. and the mechanical integrity of the delivery system and materials remained intact. When combined with intrathecal morphine or hydromorphone, no clinical evidence of drug-induced toxicity or complications was observed in any patient. Supplementing opioid therapy with bupivacaine allowed the pain patient to continue to be effectively managed using an implantable intrathecal delivery system. CONCLUSIONS: Bupivacaine is stable and compatible with a commonly used implantable drug infusion system. In this study, chronic supplementation of intrathecal opioids with bupivacaine was a safe method for providing continued management of chronic pain of cancer or noncancer origin.     

Medikamentöse Therapie bei Rückenschmerzen

Today, a wide range of efficient analgesic and non-analgesic drugs for the treatment of back pain are available. However, drugs should never be the only mainstay of a back pain treatment program. Non-steroidal antiinflammatory drugs (NSAID) are widely used in acute back pain. NSAIDs prescribed at regular intervals are effective to reduce simple back pain. The different NSAIDs are effective for the reduction of this pain. They have serious adverse effects, particularly at high doses, in the elderly, and on long-term administration. The new cyclooxygenase II-inhibitors have less gastrointestinal complications. But the long-term experiences are limited up to now. Considerable controversy exists about the use of opioid analgesics in chronic noncancer pain. Many physicians are concerned about the effectiveness and adverse effects of opioids. Other clinicians argue that there is a role for opioid therapy in chronic noncancer pain, e. g. especially in chronic low back pain. There is a low incidence of organ toxicity in patients who respond to opioids. The incidence of abuse and addiction is likewise relatively low. The potential for increased function and improved quality of life seems to outweigh the risks. However, there is a lack of randomised controlled trials (RCT) on opioid therapy in a multimodal pain treatment approach. Clinical experience and some studies suggest administration of sustained release opioids because of better comfort for the patient and less risks for addiction. The opioids should be selected due to the specific side effects of the different drugs. For patients with pre-existing constipation transdermal fentanyl should be preferred. Antidepressant medications have been used for the treatment of chronic back pain, though there is only little scientific evidence for their effectiveness. There is no evidence for the use of antidepressants in acute low back pain. Trials of muscle relaxants for patients with acute back pain have used a wide range of agents, e. g. benzodiazepines. They mostly reduce acute back pain, but they have significant adverse effects including drowsiness and psychological and physical dependence even after relatively short treatment. Benzodiazepines are not indicated in the treatment of chronic back pain. Drugs are sometimes necessary for the patients to begin and persevere a multimodal treatment program. Drug therapy should be terminated as soon as other treatment strategies succeed. Unfortunately, no studies exist evaluating the place of analgesics within a multimodal treatment program.