Anxiolytic

Anxiolytics are medications used to reduce tension, relieve anxiety or irritability, and treat insomnia. Medications used in the treatment of anxiety disorders include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), high-potency benzodiazepines (e.g., Valium), monoamine oxidase inhibitors (MAOIs), other agents (e.g., barbiturates, meprobamate, sedative-hypnotics, antihistamines, and buspirone), and combination treatments (Patterson, 2006; Preston, O’Neal, & Talaga, 2008).

Humans (and other animals) have adaptive survival mechanisms that cause them to experience fear, which can help them avoid harmful situations. For example, when confronted with a threat (e.g., coming across a rattlesnake), the body may react with increased heart rate, sweating, and other fight-or-flight responses. This adrenaline responses may increase one’s ability to escape a dangerous situation. The ability to learn what situations may be dangerous, allows individuals to avoid these situations in the future. However, when fear is out of proportion to actual threat (e.g., reacting with fear to any mention of snakes), anxiety may ensue. Avoidance learning consists of conditioned fear (an immediate response, including freezing behavior, a feeling of fear, or other reactions), which involves the brain’s amygdale, followed by an avoidance response (i.e., movement such as running away), which involves other brain structures, including the basal ganglia, frontal cortex, and hippocampus (LeDoux, 1996). Benzodiazepines enhance the effects of the neurotransmitter gamma-aminobutyric acid (GABA), an inhibitory chemical messenger that helps regulate excitability, ameliorating the conditioned fear response (LeDoux, 1996). Other anxiolytics influence the neurotransmitters serotonin and norepinephrine, which are also involved in anxiety (Patterson, 2006).

The first benzodiazepine—chlordiazepoxide (Librium)—was developed in 1957. Benzodiazepines were a significant improvement over previous anxiety medications, which included barbiturates, meprobamate (Miltown), tybamate (Solacen, Tybattam), glutethimide (Doriden), methyprylon (Noludar), and ethchlorvynol (Placidyl; Preston et al., 2008). Many of these earlier tranquilizers have high abuse potential; they can cause tolerance and severe withdrawal symptoms. The late Chief Justice William Rehnquist used Placidyl for insomnia and back pain from 1972 through 1981, when he was hospitalized for his back pain. He experienced severe withdrawal, including delusions, and had to be tapered off the drug over a period of several months (Mauro, 2007).

Benzodiazepines have both sedative and hypnotic properties. Medications with sedative properties are used to treat anxiety; hypnotics are used in the treatment of insomnia (to induce or maintain sleep). Benzodiazepines are also used as anesthetics or to aid in withdrawal from other drugs; they are fast acting and effective against anxiety. Side effects may include sedation, slurred speech, lack of coordination, and lessening of inhibitions. Some benzodiazepines (triazolam, midazolam, and lorazepam) can cause anterograde amnesia, resulting in memory loss for a period of time after the drug has worn off (Preston et al., 2008). Different benzodiazepines have varying degrees of abuse potential, physiological dependence, and withdrawal symptoms. It can be dangerous to combine benzodiazepines with alcohol; this combination is what caused Karen Ann Quinlan’s coma (Preston et al., 2008). Because many people have anxiety or insomnia, benzodiazepines have been widely used. Valium, which was introduced in 1963, became one of the best-selling pharmaceutical drugs on the marker, reaching peak sales in the United States in 1978 (Bakalar, 2005). In addition to Valium and Librium, some of the better known benzodiazepines include Xanax, Klonopin, Rohypnol, Dalmane, lorazepam (Ativan), midazolam (Versed), Restoril, and Halcion. Some of the newer atypical benzodiazepines (e.g., ProSom, quazepam) and nonbenzodiazepines (e.g., Ambien, Lunesta, Sonata) are used as hypnotics; they may be associated with less cognitive impairment, daytime fatigue, and a reduced risk of dependency (Preston et al., 2008). Benzodiazepines should not be used during pregnancy or while nursing (Preston et al., 2008).

Buspirone (BuSpar) a partial serotonin receptor (HT-1A) agonist, has anxiolytic effects and is also used as an augmentative treatment for depression. It has low potential for dependence or tolerance and fewer side effects than benzodiazepines; side effects include nausea, dizziness, and anxiety. A disadvantage of buspirone is its delayed onset of action—between one and two weeks before therapeutic benefits are experienced. It is not effective for everyone, especially people who have previously used benzodiazepines.

Some antihistamines (e.g., hydroxyzine, Benadryl) are used to treat anxiety. They cause sedation (and reduce anxiety) by blocking histamine receptors in the central nervous system. They work quickly (within 30 minutes) and last four to six hours. They are not habit forming, but they can cause drowsiness, which can make it difficult to gauge the correct therapeutic dose that will reduce anxiety without causing sedation (Preston et al., 2008). Beta blockers and clonidine are typically used to treat high blood pressure but are also effective in the treatment of some anxiety disorders. Beta blockers (e.g., atenolol, Indreral) act by blocking the effects of norepinephrine: they reduce the physical manifestations of anxiety (sweating, increased heart rate, tremor). Thus they are more effective treating periodic anxiety, such as performance anxiety, than ongoing social or generalized anxiety disorder. Side effects of beta blockers can include dizziness, low blood pressure, and depression. Clonidine (Catapres) is an alpha-2 adrenergic agonist that inhibits the release of norepinephrine. In addition to anxiety, it is also used to treat opiate withdrawal. Tiagabine (Gabitril) is a selective GABA reuptake inhibitor used as an anticonvulsant and to treat anxiety. Research has explored tiagabine’s effectiveness in the treatment of panic disorder and posttraumatic stress disorder, but more research is needed to demonstrate its efficacy (Preston et al., 2008). Some of the antidepressants are used in the treatment of anxiety. Examples include the TCA opipramol (Neuraxpharm, Insidon); the MAOI phenelzine (Nardil); SSRIs Lexapro, Luvox, Paxil, and Zoloft; serotonin-norepinephrine reuptake inhibitors (SNRI) nefazodone (Serzone) and venlafaxine (Effexor); the reversible inhibitor of monoamine oxidase A (RIMA) brofaromine (Consonat); and noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine (Remeron).

Alternative treatments used for anxiety include various herbs and medicinal plants. There is limited reliable evidence of efficacy in the treatment of anxiety with alternative treatments such as coastal water hyssop (Bacopa monnieri), kava kava (Piper methysticum), lavender (), ashwagandha (Withania somnifera; a plant in the nightshade family), passionflower (Passiflora incarnate and P. edulis), St. John’s wort (Hypericum perforatum), valerian root (Valeriana officinalis), and marijuana (Cannabis sativa). For more information about risks and benefits associated with alternative treatments; visit the National Center for Complementary and Alternative Medicine Web site.

  • LeDoux, J. (1996). The emotional brain: The mysterious underpinnings of emotional life. New York: Touchstone.
  • Preston, J.D., O’Neal, J. H., & Talaga, M.C. (2008). Handbook of clinical psychopharmacology for therapists (5th ed.). Oakland, CA: New Harbinger.
  • Since cognitive science Opens in new window has taken on board this commonsense view of the mind, an important question is how such a relationship to a proposition can be implemented.

    The representation theory of mind (RTM; Field, 1978; Fodor, 1978) assumes that a propositional attitude consists in holding a representation of the proposition and that this representation plays a certain functional role in the economy of mental states. This can be best illustrated with the two core concepts: belief and desire.

    These are core concepts, since knowing what someone believes (thinks) to be the case (e.g., Max thinking the chocolate is in the cupboard and thinking that going there will get the chocolate into his possession) and what that person desires (wants) (e.g., Max wanting the chocolate to be in his possession) allows us to make a behavioral prediction that Max will approach the cupboard. This kind of inference is known since Aristotle as the practical syllogism.

    Searle (1983, after Anscombe, 1957) points out that these two states are mirror images in terms of causal direction and direction of fit. The function of a belief is to be caused by reality and the believed proposition should match reality.

    For instance, the chocolate being in the cupboard should be responsible for Max’s believing that the chocolate is in the cupboard (world to mind causation) and the proposition “the chocolate is in the cupboard” should thus match the relevant state of affairs in the world (mind should fit world).

    The function of desire (want) is to cause a change in the world (mind to world causation) so that the world conforms to the desired proposition (world should fit mind)—for example, if Max wants the chocolate to be in the cupboard, then this desire should cause action leading to a change of the chocolate’s location such that it conforms to what Max desires.

    This trivial-sounding example does highlight the important distinctions.

    Three Important Distinctions

    1. First vs. Third Person

    One important distinction is between first-person and third-person attribution of mental states. A third-person attribution is an attribution to another person and a first-person attribution is one to myself.

    For instance, if Max erroneously believes that the chocolate is still in the cupboard (because he didn’t see that it was unexpectedly put into the drawer), then a third-person observer will attribute a false belief to Max. In contrast, Max himself will make a first-person attribution of knowledge to himself.

    The observer can capture this difference between her own and Max’s subjective view by the second-order attribution that Max thinks he knows where the chocolate is. This is useful to keep in mind when it comes to false memories. Since a memory can only be a recollection of something that actually occurred, a false memory is not a memory by third-person attribution, although it is by first-person attribution.

    1. Sense and Reference

    A related second point has to do with Frege’s (1892/1960) distinction between sense and reference. Since mental states involve representations, they connect us to objects and events in the real (or a possible) world.

    Famously, Oedipus knew and married Iocaste (referent: a particular person), but he did not know or marry her as his mother but as an unrelated queen (sense: how Iocaste was presented to Oedipus’ mind).

    Thus, in third-person parlance we can say that Oedipus married his mother if we use the expression “his mother” to pick out (refer to) the individual whom he married without implying that he knew Iocaste under that description. In first-person description of the event Oedipus would not have used the descriptor “my mother.”

    These distinctions are useful to keep in mind when discussing infants’ ability to remember particular events: Whenever a memory trace of a unique event can be demonstrated then one can conclude (in first-person parlance) as a particular event—that is, that the infant makes cognitive distinctions that represent that event as a particular event.

    1. Having vs. Representing a Mental State

    The third important distinction is that between being in a mental state (or having an attitude) and representing that mental state.

    For understanding or knowing that a person is in a mental state, or to reflect on one’s own mental states, one has to be able to represent that state. In order to be able to represent a state, one needs a concept of that state—that is, a rich enough theory of mind.

    The study of how children acquire the requisite theory of mind is therefore essential for our understanding of how children come to understand memory. Furthermore, since some memorial states are reflective or self-referential, children need a theory of mind for being in such states or having such memories.

    Why We Need a Theory of Mind for Memory

    We probably do not need a theory of mind for implicit (nondeclarative Opens in new window) memory, but for explicit (declarative Opens in new window) memory we do, since “explicit memory is revealed when performance on a task requires conscious recollection of previous experiences.” (Schacter, 1987).

    To be conscious of a fact one requires to be also aware of the state with which one beholds that fact. The higher-order-thought theories of consciousness make this their core claim (Armstrong, 1980; Rosenthal, 1986).

    For instance, if one sees a state of affairs X (e.g., that the chocolate is in the cupboard), then this seeing is a first-order mental state (attitude).

    To be conscious of this state of affairs means, according to theory, that one entertains a second-order thought about the seeing—that is, the second-order thought represents the first-order seeing.

    A weaker version does not require that one has to entertain the second-order thought, but only that one has to have the potential for having the second-order thought (Carruthers, 1996). That some such condition must be true can be seen from the following consideration:

    “Could it ever be that I can genuinely claim that I am consciously aware of the chocolate being in the cupboard, but claim ignorance of the first-order mental state by which I behold this state of affairs—that is, by claiming that I have no clue as to whether I see, or just think of, or want the chocolate being in the cupboard?”

    The important point of these conceptual analyses is that to be conscious of some fact requires some minimal concept of knowledge or of some perceptual state like seeing.

    Unfortunately, there is no clear evidence when children understand a minimal state of this sort. There is some evidence of understanding (mother’s) emotional reactions and seeing (direction of gaze) in the first year of life (see Perner, 1991, chap. 6; Baldwin & Moses, 1996; Gopnik & Meltzoff, 1997, for summaries and discussion of problems of interpretation).

    There is also some recent evidence that between 8 and 12 months children might be inferring people’s intentions to grasp an object from where that person looks (Spelke, Philips, & Woodward, 1995) and even between 5 to 9 months from how a person touches an object (seemingly intentional or accidentally).

    And by 18 months (where children’s understanding of mental phenomena seems to flourish in general) children imitate people’s intended actions even when they observe a failed attempt (Meltzoff, 1955a) and they understand differences in preferences (e.g., that someone else can prefer cauliflower over biscuits, Repacholi & Gopnik, 1997).

    Evidence that children distinguish their knowledge from ignorance is available at a relatively late age. Povinelli, Perilloux, and Bierschwale (1993) asked children to look for a sticker under one of three cups.

    Children were first trained to look under the cup at which the experimenter had pointed. After some training even the youngest were able to do this.

    When asked to look without the experimenter pointing, an interesting developmental difference emerged. Children older than 2 years and 4 months acted without hesitation when they knew which the cup the sticker was under, but hesitated noticeably when—in the absence of the experimenter’s poining—they had to guess where it was.

    Interestingly this is also the age at which children start using the phrase “I don’t know” (Shatz, Wellman, & Silber, 1983). In contrast, children younger than that showed no comparable difference in reaction time. This may indicate that young 2-year-olds do not yet reflect on what they do and do not know.

    So, theory of mind research is not yet able to give a guideline for when infants might develop explicit, conscious memories. Memory development may help out on this point.

    Meltzoff (1985, 1995b) demonstrated that 14-month-old infants can reenact a past event (e.g., they imitate the experimenter leaning forward to touch a panel with forehead so that panel lights up) after several months. Recently this has been demonstrated in 11-month-olds with a delay of 3 months.

    Since this is achieved from a brief observational period and does not require prolonged learning, and since patients with amnesia cannot do this (McDonough, Mandler, KcKee, & Squire, 1995), it is tempting to conclude that such enactment demonstrates explicit, conscious memory.

    One should, though, keep in mind that delayed imitation that is based on a single event (third-person view) is not to be equated with a memory (knowledge) of that event as a single, past event (first-person view).

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      Adapted from: The Oxford Handbook of Memory. Authored by ENDEL TULVING (ED.), Fergus I. M. Craik