检索问题
长效抗抑郁的药物有哪些？是否有长效注射药物？
目前已有多种长效抗抑郁药物可供选择，其中一些以缓释口服剂型存在，而关于长效注射药物的证据则较为有限。
长效口服抗抑郁药物
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氟西汀 (Fluoxetine):
- 一周一次的缓释剂型：氟西汀的相对长半衰期（4-6天，其活性代谢产物去甲氟西汀的半衰期更长，为4-16天）使其得以开发出每周一次的延迟释放（肠溶衣）制剂，每胶囊含90毫克氟西汀 。这种每周一次的90毫克氟西汀已被证明在维持主要抑郁症症状缓解方面与每日20毫克氟西汀同样有效和安全 。
- 患者依从性：与每日给药相比，每周一次的氟西汀能够更好地保持患者依从性 。患者普遍认为每周一次的给药方式更方便，能让他们感觉对药物的依赖性更小，并且整体上看到了更多的优点而非缺点 。
- 适应症：除了主要抑郁症的维持治疗，每周一次的氟西汀也被研究用于恐慌症的维持治疗，剂量范围为10至60毫克，已使患者在长达26个月的时间内保持无恐慌状态 。此外，肠溶衣氟西汀90毫克也已成功用于治疗经期烦躁症 (PMDD)，在黄体期每周给药一次或两次，显示出显著的疗效和良好的耐受性 。
- 副作用：每周一次的氟西汀耐受性良好，其耐受性与即释剂型相似 。与即释氟西汀相比，两种剂型的恶心发生率相似，尽管每周一次的氟西汀的血浆峰浓度更高，且峰谷浓度波动更大 。在长期治疗中，氟西汀的关键安全优势包括与三环类抗抑郁药和其他选择性血清素再摄取抑制剂 (SSRIs) 相比，不良事件和停药率较低，过量服用安全，以及在特殊人群（如孕妇）中的安全使用 。由于其长半衰期，氟西汀在中断治疗后也较少出现或仅有轻微的停药症状 。
- 代谢：氟西汀的代谢产物去甲氟西汀是比母体化合物更具选择性和更有效的5-HT再摄取抑制剂，且具有极长的半衰期（7-15天），因此该代谢产物在氟西汀的治疗效果中发挥重要作用 。
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安非他酮 (Bupropion):
- 缓释和控释剂型：安非他酮有缓释 (SR) 和控释剂型，这些剂型在减少某些不良反应方面优于其即释剂型 。
- 机制和适应症：安非他酮最初于1989年在美国获批用于治疗主要抑郁症。1997年和2000年分别在美国和英国获批用于戒烟。2006年在美国获批用于预防季节性情感障碍患者的季节性主要抑郁发作 。其主要作用机制被认为是抑制多巴胺和去甲肾上腺素的再摄取 。安非他酮及其代谢产物羟基安非他酮对生物胺再摄取的抑制作用较弱，但羟基安非他酮被认为对安非他酮的抗抑郁活性有显著贡献 。
- 戒烟效果：每日两次的缓释剂型在戒烟方面进行了广泛评估，在许多临床组别（包括健康吸烟者、心血管疾病患者、慢性阻塞性气道疾病患者、抑郁症患者和精神分裂症患者）中，一年内持续戒烟率约为20% 。
- 副作用：安非他酮的常见副作用包括失眠、头痛、口干、头晕和恶心 。与即释剂型相比，缓释和控释的安非他酮剂型与恶心总体发生率以及因恶心导致治疗中止的发生率较低相关联 。
- 药物相互作用：安非他酮是细胞色素p450 2D6抑制剂，因此在与通过该酶清除的药物以及降低癫痫发作阈值的药物共同处方时需谨慎 。
- 新复方制剂：安非他酮与右美沙芬的缓释固定复方制剂 (Auvelity) 已获批用于治疗成人主要抑郁症 。这种复方药物的常见副作用包括头晕、恶心、头痛、腹泻、嗜睡、口干、性功能障碍、多汗、焦虑、便秘、食欲下降和失眠 。所有抗抑郁药（包括右美沙芬-安非他酮）都带有黑框警告，指出其可能增加儿童和青少年患者的自杀念头和行为的风险。癫痫发作也可能发生，且在高剂量时更常见 。
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文拉法辛 (Venlafaxine):
- 缓释剂型 (XR)：文拉法辛的缓释剂型 (XR) 已被开发出来，其潜在的药代动力学优势包括降低血浆峰浓度和减少峰谷浓度波动，这可能改善药物的耐受性 。
- 副作用：文拉法辛缓释剂型与即释剂型相比，恶心发生率较低 。
- 代谢：文拉法辛及其O-去甲基文拉法辛都是5-HT和NA再摄取抑制剂，但抑制作用较弱。O-去甲基文拉法辛的清除速度比文拉法辛慢（血浆半衰期分别为5小时和11小时），可能对文拉法辛的整体治疗效果有贡献 。
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帕罗西汀 (Paroxetine):
- 控释剂型 (CR)：帕罗西汀的控释剂型 (CR) 也是一种常用的控释抗抑郁药，已显示出其优于即释剂型，能减少某些不良反应 。
- 副作用：帕罗西汀控释剂型与即释剂型相比，恶心发生率较低 。
- 机制：帕罗西汀是有效的5-HT再摄取抑制剂 。
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吉哌隆缓释片 (Gepirone Extended-Release):
- 新型缓释剂型：吉哌隆盐酸盐缓释片 (Gepirone ER) 是一种口服的、选择性5HT1A受体激动剂，设计为每日一次给药 。
- 批准：2023年9月，吉哌隆ER在美国获批用于治疗成人主要抑郁症 。
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氯胺酮缓释片 (Ketamine Extended-Release Tablets):
- 针对难治性抑郁症：外消旋氯胺酮（一种缓释片剂，R-107）已被研究用于治疗难治性主要抑郁症 (TRD)，并显示出快速起效的抗抑郁活性 。口服给药相比其他给药途径，可能改善氯胺酮的安全性和耐受性 。
- 临床试验结果：在一项2期临床试验中，患有TRD的成年患者接受每日120毫克R-107片剂，持续5天。对初始有反应的患者，随后随机接受30、60、120或180毫克R-107，每周两次，持续12周，或接受安慰剂。结果显示，180毫克片剂组在13周时的MADRS评分与安慰剂组相比有显著改善（平均差异为-6.1，P=0.019） 。
- 耐受性：该药物的耐受性良好，血压无变化，镇静和分离症状报告极少。最常见的不良事件是头痛、头晕和焦虑 。在随机阶段，大多数患者在家中进行给药 。
长效注射药物
根据提供的证据，目前没有直接提及已获批或广泛使用的长效注射抗抑郁药物。现有的长效抗抑郁药物主要是通过口服缓释或控释剂型来实现的。虽然氯胺酮的口服缓释片被提及，但尚未有证据表明有长效注射剂型在抗抑郁治疗中被常规使用或研究。
总结来看，长效抗抑郁药物主要以口服缓释或控释的形式存在，旨在提高患者依从性、改善药物耐受性并维持稳定的治疗效果。氟西汀每周一次的剂型、安非他酮的缓释/控释剂型、文拉法辛缓释剂型、帕罗西汀控释剂型以及新型的吉哌隆缓释片和氯胺酮缓释片都是这类药物的例子 。目前，关于长效注射抗抑郁药物的证据较为缺乏。
References
1Bupropion.PubMed
Scott Wilkes
Bupropion was initially developed and licensed for the treatment of major depressive disorder in the United States in 1989. It was licensed as a pharmacotherapy for smoking cessation in the United States in 1997 and in the United Kingdom in 2000, and for the prevention of seasonal major depressive episodes in patients with seasonal affective disorder in the United States in 2006. Its main mechanism of action is believed to be via dopamine and noradrenalin reuptake inhibition. In addition to proven clinical efficacy for the treatment of major depression, the prevention of depressive episodes in patients with seasonal affective disorder, and as an aid to smoking cessation treatment, bupropion has demonstrated efficacy for attenuation of symptoms of attention deficit hyperactivity disorder, and more recently it has shown anti-inflammatory action against proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may be implicated in a number of inflammatory diseases such as Crohn's disease. The twice-daily sustained-release formulation has been extensively evaluated for smoking cessation and has shown continuous smoking abstinence rates at one year of the order of 20% across many clinical groups including healthy smokers, and smokers with cardiovascular disease, chronic obstructive airways disease, depression and schizophrenia. Bupropion is well tolerated with side effects including insomnia, headache, dry mouth, dizziness and nausea. Bupropion is a cytochrome p450 2D6 inhibitor and care must be taken when coprescribing with drugs cleared by this enzyme and when coprescribing with drugs that lower seizure threshold. Despite the clinical effectiveness and cost-effectiveness of bupropion as an aid to smoking cessation, its uptake for this indication remains low when compared with nicotine replacement therapy.
2New Combination Drug for Depression.PubMed
Diane S Aschenbrenner
Auvelity, an extended-release fixed combination of dextromethorphan and bupropion, is approved for the treatment of major depressive disorder in adults.Like all antidepressants, dextromethorphan-bupropion carries a boxed warning that it may increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Seizures can also occur and are more likely at higher doses.The most common adverse effects of dextromethorphan-bupropion include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia.
3Comparative efficacy of antidepressants.PubMed
S Kasper, J Fuger, H J Möller
Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the 'standard' tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs-differences in elimination half-life (t1/2 beta) between fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging. SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)
4Once-weekly fluoxetine.PubMed
A J Wagstaff, K L Goa
The relatively long half-life of the selective serotonin reuptake inhibitor fluoxetine has allowed the development of a delayed-release (enteric-coated) formulation containing 90 mg fluoxetine per capsule for once-weekly oral administration. The cumulative relapse rate in patients switched to once-weekly fluoxetine 90 mg for 25 weeks (after responding to 13 weeks of fluoxetine 20 mg/day) was similar to that in patients continuing to receive fluoxetine 20 mg/day and significantly lower than seen in patients switched to placebo. The efficacy of the once-weekly formulation was also similar to that of the daily formulation in other assessment parameters (modified 17-item Hamilton Rating Scale for Depression, Clinical Global Impressions - Severity of Illness Scale). Patient compliance (measured using an electronically monitored tablet bottle) was maintained at 87.5% in evaluable patients receiving once-weekly fluoxetine 90 mg for 12 weeks from a baseline of 85.4% after responding to 4 weeks of fluoxetine 20 mg/day; in contrast, compliance declined significantly (from 87.3% at baseline to 79.4%; p < 0.001) in patients continuing to receive 20 mg/day for 12 weeks. Once-weekly fluoxetine is well tolerated, with a tolerability profile similar to that of the immediate-release formulation.
5Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial.PubMed
Paul Glue, Colleen Loo, Johnson Fam, et al.
Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1-8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was -6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235 .
6Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.PubMed
C Sánchez, J Hyttel
1. The present survey compares the effects of antidepressants and their principal metabolites on reuptake of biogenic amines and on receptor binding. The following antide-pressants were included in the study: the tricyclic antidepressants amitriptyline, dothiepin, and lofepramine and the atypical antidepressant bupropion, which all have considerable market shares in the UK and/or US markets; the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the recently approved antidepressants venlafaxine and nefazodone. 2. Amitriptyline has similar in vitro reuptake inhibitory potencies for 5-HT and NA, whereas the metabolite nortriptyline is preferentially a NA reuptake inhibitor. Both amitriptyline and nortriptyline are also 5-HT2 receptor antagonists. 3. Dothiepin has equipotent 5-HT and NA reuptake inhibitory activity, whereas northiaden shows a slight selectivity for NA reuptake inhibition. Dothiepin and northiaden are also 5-HT2 receptor antagonists. The slow elimination rate of northiaden (36-46 hr) compared to dothiepin (14-24 hr) suggests that northiaden contributes significantly to the therapeutic effect of dothiepin. 4. Lofepramine is extensively metabolized to desipramine. Desipramine plays an important role in the antidepressant activity of lofepramine, as the plasma elimination half-life of lofepramine (4-6 hr) is much shorter than that of desipramine (24 hr). Both compounds are potent and selective inhibitors of NA reuptake. 5. The five approved SSRIs, citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline, are potent 5-HT reuptake inhibitors, and the demethyl metabolites, norfluoxetine, demethylsertraline, and demethylcitalopram, also show selectivity. Paroxetine and sertraline are the most potent inhibitors of 5-HT reuptake, whereas citalopram is the most selective. Fluoxetine is the least selective and the metabolite of fluoxetine, norfluoxetine, is a more selective and more potent 5-HT reuptake inhibitor than the parent compound and has an extremely long half-life (7-15 compared to 1-3 days). Thus the metabolite plays an important role for the therapeutic effect of fluoxetine. Fluoxetine is also a 5-HT2C receptor antagonist. Demethylsertraline is a weaker and less selective 5-HT reuptake inhibitor in vitro than sertraline, but demethylsertraline has a very long half-life (62-104 hr) compared to the parent compound (24 hr) and it might play a role in the therapeutic effects of sertraline. Demethylcitalopram has about a 10 times lower 5-HT reuptake inhibitory potency in vitro than citalopram, and the elimination half-lives are approximately 1.5 and 2 days, respectively. 6. Bupropion and hydroxybupropion are weak inhibitors of biogenic amine reuptake. The mechanisms of action responsible for the clinical effects of bupropion are not fully understood, but it has been suggested that both dopaminergic and noradrenergic components play a role and that the hydroxybupropion metabolite contributes significantly to the antidepressant activity. 7. Venlafaxine and O-demethylvenlafaxine are weak inhibitors of 5-HT and NA reuptake, and the selectivity ratios are close to one. O-Demethylvenlafaxine is eliminated more slowly than venlafaxine (plasma half-lives of 5 and 11 hr, respectively), and it is likely that it contributes to the overall therapeutic effect of venlafaxin. 8. Nefazodone and alpha-hydroxynefazodone are equipotent 5-HT and NA reuptake inhibitors. Both compounds are also 5-HT2 receptor antagonists. Both parent compound and metabolite have short elimination half-lives.
7Patient perspectives on once-weekly fluoxetine.PubMed
R Judge
BACKGROUND: Continuation therapy is recommended for 4 to 9 months following remission of symptoms of major depressive disorder. Long-term maintenance therapy is recommended for patients with severe, recurrent symptoms. However, most patients do not complete an adequate course of therapy. We investigated patient perceptions of antidepressant dosing to determine whether weekly dosing could provide an additional tool to help more patients remain compliant with antidepressant treatment. METHOD: Physicians were asked to complete an anonymous patient profile for 7 patients currently receiving antidepressant treatment and to give those patients a questionnaire that the patients could submit anonymously. In addition, clinically depressed patients in the United States and in France were surveyed by telephone. RESULTS: Patients surveyed by questionnaire agreed most strongly with statements indicating that they would like their doctor to involve them in the choice of antidepressant medication, that they did not want others to know they were taking antidepressant medication, and that they disliked the idea of taking daily medication. Patients in the telephone survey agreed most strongly with statements indicating that they considered once-weekly dosing more convenient than daily dosing, that they believed taking 1 pill a week would make them feel less dependent on pills, and that they perceived more advantages than disadvantages in taking 1 pill a week. CONCLUSION: Weekly antidepressant treatment may provide an effective tool in helping patients with depression. Positive patient perceptions of weekly dosing suggest that some patients may remain on continuation or maintenance therapy longer when they have the option of weekly dosing.
8Improving antidepressant adherence.PubMed
Charles B Nemeroff
Frequently, patients suffering from depressive disorders discontinue antidepressant treatment due to the unpleasant side effects of these medications, particularly in the first month of therapy. Good tolerability (particularly in the early stages of treatment), patient education, and the quality of the relationship between physicians and patients are all common determining factors of patient adherence. Controlled-release antidepressant agents have the potential to improve tolerability early in the course of therapy, one of the most likely periods of dropout from treatment. Side effects for controlled-release formulations are often more favorable because controlled-release formulations exhibit lower peak plasma drug concentrations when compared with immediate-release formulations. Venlafaxine extended-release (XR), bupropion sustained-release (SR), and paroxetine controlled-release (CR) are 3 commonly utilized controlled-release antidepressants that have demonstrated improvement over their immediate-release predecessors in reducing certain adverse effects.
9Fluoxetine: a suitable long-term treatment.PubMed
H M Calil
A review of fluoxetine's safety profile, especially during long-term treatment, is presented. Key safety advantages for fluoxetine include lower adverse events and dropout rates compared with tricyclic antidepressants and other selective serotonin reuptake inhibitors (SSRIs), safety in overdose, and safe use in special population groups such as women in pregnancy. Prospectively ascertained pregnancy outcomes following exposure to SSRIs, mainly fluoxetine, consistently show no teratogenic effects as assessed in the postnatal period and in comparison with controls. An additional advantage of fluoxetine is the absence or mildness of discontinuation symptoms following treatment interruption, probably a consequence of fluoxetine's long half-life in comparison with other SSRIs. The available data on these topics confirm the suitability of long-term fluoxetine treatment.
10Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea.PubMed
C Lindsay DeVane
Newer antidepressants are generally as efficacious as but often have fewer side effects than their predecessors such as the tricyclic antidepressants and monoamine oxidase inhibitors. These newer antidepressants include the selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; venlafaxine, a serotonin-norepinephrine reuptake inhibitor; and bupropion, a selective norepinephrine and dopamine reuptake inhibitor. Most of these antidepressants have half-lives that enable them to be administered as infrequently as 1 to 3 times per day. To further improve upon the ease of use, controlled-release formulations of bupropion, fluoxetine, paroxetine, and venlafaxine have been manufactured. Potential pharmacokinetic advantages of these formulations include lower peak plasma drug concentrations and smaller fluctuations between peak and trough plasma drug concentrations, which might influence the tolerability of these medications. Tolerability advantages seen with some of these medications include diminished nausea. The 3 controlled-release agents that are designed to be taken daily--bupropion, paroxetine, and venlafaxine--are associated with lower incidences of nausea overall and nausea leading to treatment discontinuation than are their immediate-release formulations. However, the rates of nausea are similar with both formulations of fluoxetine, despite higher peak plasma drug concentrations and greater fluctuation between peak and trough plasma drug concentrations with fluoxetine weekly than with fluoxetine daily. Although the connection has not been proven, more stable pharmacokinetic profiles might be the cause for the low occurrence of nausea with some controlled-release newer antidepressants.
11Gepirone Extended-Release: First Approval.PubMed
Susan J Keam
Gepirone HCL extended-release (gepirone ER; EXXUA™), an oral, selective serotonin (5HT)1A receptor agonist formulated for once-daily administration, has been developed by Fabre-Kramer Pharmaceuticals, Inc. for the treatment of psychiatric disorders, including major depressive disorder (MDD). In September 2023, gepirone ER was approved in the USA for the treatment of adults with MDD. This article summarizes the milestones in the development of gepirone ER leading to this first approval for the treatment of adults with MDD.
12Higher dose weekly fluoxetine in hemodialysis patients: A case series report.PubMed
Kelley M Kauffman, Jacqueline Dolata, Maria Figueroa, et al.
OBJECTIVE: The antidepressant medication fluoxetine at 90 mg dosed weekly is as effective and safe as standard formulation fluoxetine 20 mg dosed daily in patients with major depressive disorder. Weekly fluoxetine has not been well studied in hemodialysis patients, and doses beyond 90 mg/week have not been described in this population. This case series, derived from a larger study on depression in hemodialysis patients, describes the use of weekly fluoxetine at dosages beyond 90 mg/week. METHOD: Hemodialysis patients with depressive symptom severity scored ≥10 on the 9-item Patient Health Questionnaire and major depressive disorder confirmed with Mini International Neuropsychiatric Interview were initially prescribed daily fluoxetine for two weeks and then transitioned to weekly fluoxetine. Dosage titration was made at the discretion of the prescribing clinician. Fluoxetine was continued for a total of 12 weeks. RESULTS: Four women, aged 24 to 65 years, on hemodialysis for 1 to 18 years, were started on weekly fluoxetine that was increased over several weeks up to 180 mg. Side effects included restlessness, dry mouth, sedation, and lightheadedness. Two patients ultimately had their weekly fluoxetine decreased back to 90 mg. However, all four continued weekly fluoxetine as part of poststudy aftercare and no longer met diagnostic criteria for major depressive disorder, current episode. CONCLUSIONS: Weekly fluoxetine at doses of 180 mg may be a reasonable treatment consideration for hemodialysis patients who have partial or insufficient antidepressant response. Side effects may limit tolerance of the 180 mg dose in some individuals. Future research should investigate longer term health outcomes of weekly fluoxetine in this population.
13Once-weekly dosing of fluoxetine in the maintenance of remission in panic disorder.PubMed
N P Emmanuel, M R Ware, O Brawman-Mintzer, et al.
BACKGROUND: Fluoxetine and its active metabolite norfluoxetine have long half-lives of 4-6 days and 4-16 days, respectively. We postulated that, owing to the long elimination half-life, patients diagnosed with panic disorder might be maintained on fluoxetine taken once a week, after being treated initially with daily doses of fluoxetine. METHOD: Ten patients with DSM-III-R panic disorder were treated openly with fluoxetine, 20-40 mg daily. Once panic free, these patients were switched to once-weekly dosing of fluoxetine, and dosage was titrated as needed. RESULTS: All 10 patients successfully switched to once-weekly dosing. One patient reported recurrence of panic attacks 18 months after the switch. After a brief treatment for 4 weeks with benzodiazepines and daily fluoxetine, the patient was once again maintained on once-weekly dosing when rechallenged. Patients have been maintained in a panic-free state for up to 26 months with a single weekly dose of fluoxetine ranging from 10 to 60 mg. The medication was well tolerated. CONCLUSION: Fluoxetine at doses ranging from 10 to 60 mg administered once weekly appears to be effective maintenance treatment for patients with panic disorder who were initially treated successfully with daily fluoxetine. A once-weekly regimen may allow for considerable cost savings and may serve as a convenient alternative method for treating panic disorder.
14Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial.PubMed
Cherri Miner, Eileen Brown, Susan McCray, et al.
BACKGROUND: Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized. OBJECTIVE: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD. METHODS: Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale. RESULTS: Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups. CONCLUSION: The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD.
15New formulations of existing antidepressants: advantages in the management of depression.PubMed
Trevor R Norman, James S Olver
For nearly 50 years, antidepressant drugs have been the first-line treatment for various forms of depression. Despite their widespread use, these medications have significant shortcomings, in particular problems of patient compliance due to adverse effects. The introduction of new formulations of existing antidepressant medications may provide patients with benefits in terms of convenience of use. As a consequence, improvements in compliance may lead to better antidepressant efficiency.An orally disintegrating formulation of mirtazapine (mirtazapine SolTab), a once-weekly formulation of fluoxetine, an enantiomer-specific formulation of citalopram (escitalopram), an extended-release formulation of venlafaxine (venlafaxine XR), a controlled-release formulation of paroxetine (paroxetine CR) and intravenous formulations of some of the newer antidepressants have all been evaluated in limited clinical trials. In this article, a review of the pharmacokinetics and clinical evaluations of these formulations is presented. While there do not appear to be major clinical advantages for the new formulations in terms of antidepressant efficacy, none of them is less efficacious than their older counterpart. Indeed, some of the new formulations are more acceptable to patients (fluoxetine once-weekly, paroxetine CR), others have pharmacokinetic advantages (venlafaxine XR, paroxetine CR), while others may have a faster onset of effect (mirtazapine SolTab, intravenous formulations). Further evaluation of some formulations is still required (mirtazapine SolTab, fluoxetine once-weekly), while others (venlafaxine XR, escitalopram) are finding widespread acceptance in clinical practice.